The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Qinglong Guo - One of the best experts on this subject based on the ideXlab platform.
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Wogonin suppresses human alveolar adenocarcinoma cell a549 migration in inflammatory microenvironment by modulating the il 6 stat3 signaling pathway
Molecular Carcinogenesis, 2015Co-Authors: Yue Zhao, Qidong You, Li Zhao, Jing Yao, Yuxin Zhou, Yi Zhang, Qinglong GuoAbstract:Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment facilitates tumor metastasis. Clinically, it will be a promising choice to suppress tumor metastasis by targeting inflammatory microenvironment. Our previous studies have demonstrated that Wogonin (a bioflavonoid isolated from the traditional Chinese medicine of Huang-Qin) possesses the anti-metastatic and anti-inflammatory activity, but we have little idea about its efficacy on inflammatory-induced tumor metastasis and the mechanism underlying it. In this study, we focused on epithelial mesenchymal transition (EMT), the first step of tumor metastasis, to evaluate the effects of Wogonin on tumor metastasis in inflammatory microenvironment. We found that Wogonin inhibited THP-1 conditioned-medium- (CM-) and IL-6-induced EMT by inactivating STAT3 signal. And in Wogonin-treated A549 cells which pretreated with THP-1 CM or IL-6, the expression level of E-cadherin, an EMT negative biomarker, increased while that of N-cadherin, Vimentin, and EMT-related transcription factors including Snail and Twist decreased. Moreover, Wogonin inhibited IL-6-induced phosphorylation of STAT3, prevented p-STAT3 dimer translocation into the nucleus, and suppressed the DNA-binding activity of p-STAT3. Interestingly, similar results were obtained in the tumor xenografts mice, including downregulation of p-STAT3, N-cadherin, and Vimentin while up-regulation of E-cadherin. Wogonin also inhibit the metastasis of A549 cells in vivo. Taken all data together, we concluded that Wogonin suppresses tumor cells migration in inflammatory microenvironment by inactivating STAT3 signal. © 2014 Wiley Periodicals, Inc.
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Wogonin reverses multi drug resistance of human myelogenous leukemia k562 a02 cells via downregulation of mrp1 expression by inhibiting nrf2 are signaling pathway
Biochemical Pharmacology, 2014Co-Authors: Yi Zhang, Qidong You, Li Zhao, Yuxin Zhou, Haiwei Zhang, Hanchi Miao, Qinglong GuoAbstract:Constitutive NF-E2-related factor 2 (Nrf2) activation has been recently reported to play a pivotal role in enhancing cell survival and resistance to anticancer drugs in many tumors. Previously, much effort has been devoted to the investigation of blocking Nrf2 function in cultured cells and cancer tissues, but few researches have been undertaken to evaluate the precise mechanism of flavonoids-induced sensitivity by inhibiting Nrf2. In this study, we investigated the reversal effect of Wogonin, a flavonoid isolated from the root of Scutellaria baicalensis Georgi, in resistant human myelogenous leukemia. Data indicated that Wogonin had strong reversal potency by inhibiting functional activity and expression of MRP1 at both protein and mRNA in adriamycin (ADR)-induced resistant human myelogenous leukemia K562/A02 cells. Consequently, the inhibition of MRP1 by Wogonin was dependent on Nrf2 through the decreased binding ability of Nrf2 to antioxidant response element (ARE). Further research revealed Wogonin modulated Nrf2 through the reduction of Nrf2mRNA at transcriptional processes rather than RNA degradation, which is regulated by the PI3K/Akt pathway. Moreover, DNA-PKcs was found to be involved in the Wogonin-induced downregulation of Nrf2 mRNA at transcriptional levels. In summary, these results clearly demonstrated the effectiveness of using Wogonin via inhibiting Nrf2 to combat chemoresistance and suggested that Wogonin can be developed into an efficient natural sensitizer for resistant human myelogenous leukemia.
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Wogonin prevents lipopolysaccharide induced acute lung injury and inflammation in mice via peroxisome proliferator activated receptor gamma mediated attenuation of the nuclear factor kappab pathway
Immunology, 2014Co-Authors: Jing Yao, Qidong You, Li Zhao, Yue Zhao, Di Pan, Jie Sun, Yu Wang, Qinglong GuoAbstract:Acute lung injury (ALI) from a variety of clinical disorders, characterized by diffuse inflammation, is a cause of acute respiratory failure that develops in patients of all ages. Previous studies reported that Wogonin, a flavonoid-like chemical compound which was found in Scutellaria baicalensis, has anti-inflammatory effects in several inflammation models, but not in ALI. Here, the in vivo protective effect of Wogonin in the amelioration of lipopolysaccharide (LPS) -induced lung injury and inflammation was assessed. In addition, the in vitro effects and mechanisms of Wogonin were studied in the mouse macrophage cell lines Ana-1 and RAW264.7. In vivo results indicated that Wogonin attenuated LPS-induced histological alterations. Peripheral blood leucocytes decreased in the LPS-induced group, which was ameliorated by Wogonin. In addition, Wogonin inhibited the production of several inflammatory cytokines, including tumour necrosis factor-α, interleukin-1β (IL-1β) and IL-6, in the bronchoalveolar lavage fluid and lung tissues after LPS challenge, while the peroxisome proliferator-activated receptor γ (PPARγ) inhibitor GW9662 reversed these effects. In vitro results indicated that Wogonin significantly decreased the secretion of IL-6, IL-1β and tumour necrosis factor-α in Ana-1 and RAW264.7 cells, which was suppressed by transfection of PPARγ small interfering RNA and GW9662 treatment. Moreover, Wogonin activated PPARγ, induced PPARγ-mediated attenuation of the nuclear translocation and the DNA-binding activity of nuclear factor-κB in vivo and in vitro. In conclusion, all of these results showed that Wogonin may serve as a promising agent for the attenuation of ALI-associated inflammation and pathology by regulating the PPARγ-involved nuclear factor-κB pathway.
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Wogonin suppresses melanoma cell b16 f10 invasion and migration by inhibiting ras medicated pathways
PLOS ONE, 2014Co-Authors: Kai Zhao, Qidong You, Libin Wei, Hui Hui, Qinsheng Dai, Qinglong GuoAbstract:The patients diagnosed with melanoma have a bad prognosis for early regional invasion and distant metastases. Wogonin (5,7-dihydroxy-8-methoxyflavone) is one of the active components of flavonoids that extracts from Scutellariae radix. Several previous studies reported that Wogonin possesses antitumor effect against leukemia, gastrointestinal cancer and breast cancer. In this study, we used melanoma cell B16-F10 to further investigate the anti-invasive and anti-migratory activity of Wogonin. Our date showed that Wogonin caused suppression of cell migration, adhesion, invasion and actin remodeling by inhibiting the expression of matrix metalloproteinase-2 and Rac1 in vitro. Wogonin also reduced the number of the tumor nodules on the whole surface of the lung in vivo. Furthermore, the examination of mechanism revealed that Wogonin inhibited Extracellular Regulated protein Kinases and Protein Kinase B pathways, which are both medicated by Ras. Insulin-like growth factor-1-induced or tumor necrosis factor-α-induced invasion was also inhibited by Wogonin. Therefore, the inhibitory mechanism of melanoma cell invasion by Wogonin might be elucidated.
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Wogonin inhibits lps induced tumor angiogenesis via suppressing pi3k akt nf κb signaling
European Journal of Pharmacology, 2014Co-Authors: Kai Zhao, Qidong You, Xiuming Song, Jing Yao, Mi Zhou, Yujie Huang, Qinglong GuoAbstract:Wogonin has been shown to have anti-angiogenesis and anti-tumor effects. However, whether Wogonin inhibits LPS-induced tumor angiogenesis is not well known. In this study, we investigated the effect of Wogonin on inhibiting LPS-induced tumor angiogenesis and further probed the underlying mechanisms. ELISA results revealed that Wogonin could suppress LPS-induced VEGF secretion from tumor cells. Transwell assay, tube formation assay, rat aortic ring assay and CAM model were used to evaluate the effect of Wogonin on angiogenesis induced by MCF-7 cell (treated with LPS) in vitro and in vivo. The inhibitory effect of Wogonin on angiogenesis in LPS-treated MCF-7 cells was then confirmed by the above in vitro and in vivo assays. The study of the molecular mechanism showed that Wogonin could suppress PI3K/Akt signaling activation. Moreover, Wogonin inhibited nuclear translocation of NF-κB and its binding to DNA. The result of real-time PCR and luciferase reporter assay suggested that VEGF expression was down-regulated by Wogonin primarily at the transcriptional level. IGF-1 and p65 expression plasmid were used to activate PI3K/Akt and NF-κB pathways, and to observe the effect of Wogonin on the simualtion of PI3K/Akt/NF-κB signaling. Taken together, the result suggested that Wogonin was a potent inhibitor of tumor angiogenesis and provided a new insight into the mechanisms of Wogonin against cancer.
Qidong You - One of the best experts on this subject based on the ideXlab platform.
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Wogonin suppresses human alveolar adenocarcinoma cell a549 migration in inflammatory microenvironment by modulating the il 6 stat3 signaling pathway
Molecular Carcinogenesis, 2015Co-Authors: Yue Zhao, Qidong You, Li Zhao, Jing Yao, Yuxin Zhou, Yi Zhang, Qinglong GuoAbstract:Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment facilitates tumor metastasis. Clinically, it will be a promising choice to suppress tumor metastasis by targeting inflammatory microenvironment. Our previous studies have demonstrated that Wogonin (a bioflavonoid isolated from the traditional Chinese medicine of Huang-Qin) possesses the anti-metastatic and anti-inflammatory activity, but we have little idea about its efficacy on inflammatory-induced tumor metastasis and the mechanism underlying it. In this study, we focused on epithelial mesenchymal transition (EMT), the first step of tumor metastasis, to evaluate the effects of Wogonin on tumor metastasis in inflammatory microenvironment. We found that Wogonin inhibited THP-1 conditioned-medium- (CM-) and IL-6-induced EMT by inactivating STAT3 signal. And in Wogonin-treated A549 cells which pretreated with THP-1 CM or IL-6, the expression level of E-cadherin, an EMT negative biomarker, increased while that of N-cadherin, Vimentin, and EMT-related transcription factors including Snail and Twist decreased. Moreover, Wogonin inhibited IL-6-induced phosphorylation of STAT3, prevented p-STAT3 dimer translocation into the nucleus, and suppressed the DNA-binding activity of p-STAT3. Interestingly, similar results were obtained in the tumor xenografts mice, including downregulation of p-STAT3, N-cadherin, and Vimentin while up-regulation of E-cadherin. Wogonin also inhibit the metastasis of A549 cells in vivo. Taken all data together, we concluded that Wogonin suppresses tumor cells migration in inflammatory microenvironment by inactivating STAT3 signal. © 2014 Wiley Periodicals, Inc.
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Wogonin reverses multi drug resistance of human myelogenous leukemia k562 a02 cells via downregulation of mrp1 expression by inhibiting nrf2 are signaling pathway
Biochemical Pharmacology, 2014Co-Authors: Yi Zhang, Qidong You, Li Zhao, Yuxin Zhou, Haiwei Zhang, Hanchi Miao, Qinglong GuoAbstract:Constitutive NF-E2-related factor 2 (Nrf2) activation has been recently reported to play a pivotal role in enhancing cell survival and resistance to anticancer drugs in many tumors. Previously, much effort has been devoted to the investigation of blocking Nrf2 function in cultured cells and cancer tissues, but few researches have been undertaken to evaluate the precise mechanism of flavonoids-induced sensitivity by inhibiting Nrf2. In this study, we investigated the reversal effect of Wogonin, a flavonoid isolated from the root of Scutellaria baicalensis Georgi, in resistant human myelogenous leukemia. Data indicated that Wogonin had strong reversal potency by inhibiting functional activity and expression of MRP1 at both protein and mRNA in adriamycin (ADR)-induced resistant human myelogenous leukemia K562/A02 cells. Consequently, the inhibition of MRP1 by Wogonin was dependent on Nrf2 through the decreased binding ability of Nrf2 to antioxidant response element (ARE). Further research revealed Wogonin modulated Nrf2 through the reduction of Nrf2mRNA at transcriptional processes rather than RNA degradation, which is regulated by the PI3K/Akt pathway. Moreover, DNA-PKcs was found to be involved in the Wogonin-induced downregulation of Nrf2 mRNA at transcriptional levels. In summary, these results clearly demonstrated the effectiveness of using Wogonin via inhibiting Nrf2 to combat chemoresistance and suggested that Wogonin can be developed into an efficient natural sensitizer for resistant human myelogenous leukemia.
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Wogonin prevents lipopolysaccharide induced acute lung injury and inflammation in mice via peroxisome proliferator activated receptor gamma mediated attenuation of the nuclear factor kappab pathway
Immunology, 2014Co-Authors: Jing Yao, Qidong You, Li Zhao, Yue Zhao, Di Pan, Jie Sun, Yu Wang, Qinglong GuoAbstract:Acute lung injury (ALI) from a variety of clinical disorders, characterized by diffuse inflammation, is a cause of acute respiratory failure that develops in patients of all ages. Previous studies reported that Wogonin, a flavonoid-like chemical compound which was found in Scutellaria baicalensis, has anti-inflammatory effects in several inflammation models, but not in ALI. Here, the in vivo protective effect of Wogonin in the amelioration of lipopolysaccharide (LPS) -induced lung injury and inflammation was assessed. In addition, the in vitro effects and mechanisms of Wogonin were studied in the mouse macrophage cell lines Ana-1 and RAW264.7. In vivo results indicated that Wogonin attenuated LPS-induced histological alterations. Peripheral blood leucocytes decreased in the LPS-induced group, which was ameliorated by Wogonin. In addition, Wogonin inhibited the production of several inflammatory cytokines, including tumour necrosis factor-α, interleukin-1β (IL-1β) and IL-6, in the bronchoalveolar lavage fluid and lung tissues after LPS challenge, while the peroxisome proliferator-activated receptor γ (PPARγ) inhibitor GW9662 reversed these effects. In vitro results indicated that Wogonin significantly decreased the secretion of IL-6, IL-1β and tumour necrosis factor-α in Ana-1 and RAW264.7 cells, which was suppressed by transfection of PPARγ small interfering RNA and GW9662 treatment. Moreover, Wogonin activated PPARγ, induced PPARγ-mediated attenuation of the nuclear translocation and the DNA-binding activity of nuclear factor-κB in vivo and in vitro. In conclusion, all of these results showed that Wogonin may serve as a promising agent for the attenuation of ALI-associated inflammation and pathology by regulating the PPARγ-involved nuclear factor-κB pathway.
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Wogonin suppresses melanoma cell b16 f10 invasion and migration by inhibiting ras medicated pathways
PLOS ONE, 2014Co-Authors: Kai Zhao, Qidong You, Libin Wei, Hui Hui, Qinsheng Dai, Qinglong GuoAbstract:The patients diagnosed with melanoma have a bad prognosis for early regional invasion and distant metastases. Wogonin (5,7-dihydroxy-8-methoxyflavone) is one of the active components of flavonoids that extracts from Scutellariae radix. Several previous studies reported that Wogonin possesses antitumor effect against leukemia, gastrointestinal cancer and breast cancer. In this study, we used melanoma cell B16-F10 to further investigate the anti-invasive and anti-migratory activity of Wogonin. Our date showed that Wogonin caused suppression of cell migration, adhesion, invasion and actin remodeling by inhibiting the expression of matrix metalloproteinase-2 and Rac1 in vitro. Wogonin also reduced the number of the tumor nodules on the whole surface of the lung in vivo. Furthermore, the examination of mechanism revealed that Wogonin inhibited Extracellular Regulated protein Kinases and Protein Kinase B pathways, which are both medicated by Ras. Insulin-like growth factor-1-induced or tumor necrosis factor-α-induced invasion was also inhibited by Wogonin. Therefore, the inhibitory mechanism of melanoma cell invasion by Wogonin might be elucidated.
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Wogonin inhibits lps induced tumor angiogenesis via suppressing pi3k akt nf κb signaling
European Journal of Pharmacology, 2014Co-Authors: Kai Zhao, Qidong You, Xiuming Song, Jing Yao, Mi Zhou, Yujie Huang, Qinglong GuoAbstract:Wogonin has been shown to have anti-angiogenesis and anti-tumor effects. However, whether Wogonin inhibits LPS-induced tumor angiogenesis is not well known. In this study, we investigated the effect of Wogonin on inhibiting LPS-induced tumor angiogenesis and further probed the underlying mechanisms. ELISA results revealed that Wogonin could suppress LPS-induced VEGF secretion from tumor cells. Transwell assay, tube formation assay, rat aortic ring assay and CAM model were used to evaluate the effect of Wogonin on angiogenesis induced by MCF-7 cell (treated with LPS) in vitro and in vivo. The inhibitory effect of Wogonin on angiogenesis in LPS-treated MCF-7 cells was then confirmed by the above in vitro and in vivo assays. The study of the molecular mechanism showed that Wogonin could suppress PI3K/Akt signaling activation. Moreover, Wogonin inhibited nuclear translocation of NF-κB and its binding to DNA. The result of real-time PCR and luciferase reporter assay suggested that VEGF expression was down-regulated by Wogonin primarily at the transcriptional level. IGF-1 and p65 expression plasmid were used to activate PI3K/Akt and NF-κB pathways, and to observe the effect of Wogonin on the simualtion of PI3K/Akt/NF-κB signaling. Taken together, the result suggested that Wogonin was a potent inhibitor of tumor angiogenesis and provided a new insight into the mechanisms of Wogonin against cancer.
Li Zhao - One of the best experts on this subject based on the ideXlab platform.
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Wogonin suppresses human alveolar adenocarcinoma cell a549 migration in inflammatory microenvironment by modulating the il 6 stat3 signaling pathway
Molecular Carcinogenesis, 2015Co-Authors: Yue Zhao, Qidong You, Li Zhao, Jing Yao, Yuxin Zhou, Yi Zhang, Qinglong GuoAbstract:Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment facilitates tumor metastasis. Clinically, it will be a promising choice to suppress tumor metastasis by targeting inflammatory microenvironment. Our previous studies have demonstrated that Wogonin (a bioflavonoid isolated from the traditional Chinese medicine of Huang-Qin) possesses the anti-metastatic and anti-inflammatory activity, but we have little idea about its efficacy on inflammatory-induced tumor metastasis and the mechanism underlying it. In this study, we focused on epithelial mesenchymal transition (EMT), the first step of tumor metastasis, to evaluate the effects of Wogonin on tumor metastasis in inflammatory microenvironment. We found that Wogonin inhibited THP-1 conditioned-medium- (CM-) and IL-6-induced EMT by inactivating STAT3 signal. And in Wogonin-treated A549 cells which pretreated with THP-1 CM or IL-6, the expression level of E-cadherin, an EMT negative biomarker, increased while that of N-cadherin, Vimentin, and EMT-related transcription factors including Snail and Twist decreased. Moreover, Wogonin inhibited IL-6-induced phosphorylation of STAT3, prevented p-STAT3 dimer translocation into the nucleus, and suppressed the DNA-binding activity of p-STAT3. Interestingly, similar results were obtained in the tumor xenografts mice, including downregulation of p-STAT3, N-cadherin, and Vimentin while up-regulation of E-cadherin. Wogonin also inhibit the metastasis of A549 cells in vivo. Taken all data together, we concluded that Wogonin suppresses tumor cells migration in inflammatory microenvironment by inactivating STAT3 signal. © 2014 Wiley Periodicals, Inc.
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Wogonin reverses multi drug resistance of human myelogenous leukemia k562 a02 cells via downregulation of mrp1 expression by inhibiting nrf2 are signaling pathway
Biochemical Pharmacology, 2014Co-Authors: Yi Zhang, Qidong You, Li Zhao, Yuxin Zhou, Haiwei Zhang, Hanchi Miao, Qinglong GuoAbstract:Constitutive NF-E2-related factor 2 (Nrf2) activation has been recently reported to play a pivotal role in enhancing cell survival and resistance to anticancer drugs in many tumors. Previously, much effort has been devoted to the investigation of blocking Nrf2 function in cultured cells and cancer tissues, but few researches have been undertaken to evaluate the precise mechanism of flavonoids-induced sensitivity by inhibiting Nrf2. In this study, we investigated the reversal effect of Wogonin, a flavonoid isolated from the root of Scutellaria baicalensis Georgi, in resistant human myelogenous leukemia. Data indicated that Wogonin had strong reversal potency by inhibiting functional activity and expression of MRP1 at both protein and mRNA in adriamycin (ADR)-induced resistant human myelogenous leukemia K562/A02 cells. Consequently, the inhibition of MRP1 by Wogonin was dependent on Nrf2 through the decreased binding ability of Nrf2 to antioxidant response element (ARE). Further research revealed Wogonin modulated Nrf2 through the reduction of Nrf2mRNA at transcriptional processes rather than RNA degradation, which is regulated by the PI3K/Akt pathway. Moreover, DNA-PKcs was found to be involved in the Wogonin-induced downregulation of Nrf2 mRNA at transcriptional levels. In summary, these results clearly demonstrated the effectiveness of using Wogonin via inhibiting Nrf2 to combat chemoresistance and suggested that Wogonin can be developed into an efficient natural sensitizer for resistant human myelogenous leukemia.
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Wogonin prevents lipopolysaccharide induced acute lung injury and inflammation in mice via peroxisome proliferator activated receptor gamma mediated attenuation of the nuclear factor kappab pathway
Immunology, 2014Co-Authors: Jing Yao, Qidong You, Li Zhao, Yue Zhao, Di Pan, Jie Sun, Yu Wang, Qinglong GuoAbstract:Acute lung injury (ALI) from a variety of clinical disorders, characterized by diffuse inflammation, is a cause of acute respiratory failure that develops in patients of all ages. Previous studies reported that Wogonin, a flavonoid-like chemical compound which was found in Scutellaria baicalensis, has anti-inflammatory effects in several inflammation models, but not in ALI. Here, the in vivo protective effect of Wogonin in the amelioration of lipopolysaccharide (LPS) -induced lung injury and inflammation was assessed. In addition, the in vitro effects and mechanisms of Wogonin were studied in the mouse macrophage cell lines Ana-1 and RAW264.7. In vivo results indicated that Wogonin attenuated LPS-induced histological alterations. Peripheral blood leucocytes decreased in the LPS-induced group, which was ameliorated by Wogonin. In addition, Wogonin inhibited the production of several inflammatory cytokines, including tumour necrosis factor-α, interleukin-1β (IL-1β) and IL-6, in the bronchoalveolar lavage fluid and lung tissues after LPS challenge, while the peroxisome proliferator-activated receptor γ (PPARγ) inhibitor GW9662 reversed these effects. In vitro results indicated that Wogonin significantly decreased the secretion of IL-6, IL-1β and tumour necrosis factor-α in Ana-1 and RAW264.7 cells, which was suppressed by transfection of PPARγ small interfering RNA and GW9662 treatment. Moreover, Wogonin activated PPARγ, induced PPARγ-mediated attenuation of the nuclear translocation and the DNA-binding activity of nuclear factor-κB in vivo and in vitro. In conclusion, all of these results showed that Wogonin may serve as a promising agent for the attenuation of ALI-associated inflammation and pathology by regulating the PPARγ-involved nuclear factor-κB pathway.
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nf κb and nrf2 signaling pathways contribute to Wogonin mediated inhibition of inflammation associated colorectal carcinogenesis
Cell Death and Disease, 2014Co-Authors: Jingyue Yao, Qidong You, Li Zhao, Yue Zhao, Qing Zhao, Yang Sun, Yameng Zhang, Hanchi Miao, Qinglong GuoAbstract:The transcriptional factors nuclear factor-κB (NF-κB) and NF-E2-related factor 2 (Nrf2) have been recently reported to have critical roles in protecting various tissues against inflammation and colitis-associated colorectal cancer (aberrant crypt foci). Our previous studies showed that Wogonin (5,7-dihydroxy-8-methoxyflavone) possessed anti-neoplastic and anti-inflammatory activities. The present study extended these important earlier findings by exploring the effect of Wogonin on the initiation and development of colitis-associated cancer. Wogonin lowered tumor incidence and inhibited the development of colorectal adenomas in azoxymethane- or dextran sulfate sodium-induced mice. We found that Wogonin significantly decreased the secretion and expression of IL-6 and IL-1β, reduced cell proliferation and nuclear expression of NF-κB in adenomas and surrounding tissues and promoted Nrf2 nuclear translocation in surrounding tissues, although overexpressed Nrf2 in tumor tissues was independent of Wogonin administration. Furthermore, Wogonin inhibited the interaction between human monocytic THP-1 cells and human colon cancer HCT116 cells, and significantly downregulated lipopolysaccharide-induced secretion of prototypical pro-inflammatory cytokines IL-6 and IL-1β in THP-1 cells. Further mechanism research revealed that Wogonin inhibited the nuclear translocation of NF-κB and phosphorylation of IκB and IKKα/β, and promoted Nrf2 signaling pathway in HCT116 cells and THP-1 cells. Taken together, the present results indicated that Wogonin effectively suppressed inflammation-associated colon carcinogenesis and cancer development, suggesting its potential as a chemopreventive agent against colitis-associated colon cancer.
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Wogonin reverses hypoxia resistance of human colon cancer hct116 cells via downregulation of hif 1α and glycolysis by inhibiting pi3k akt signaling pathway
Molecular Carcinogenesis, 2014Co-Authors: Hu Wang, Qidong You, Li Zhao, Jing Yao, Di Pan, Yu Wang, Litao Zhu, Qinglong GuoAbstract:Hypoxia induced drug resistance is a major obstacle in the development of effective cancer therapy. In the present study, the reversal abilities of Wogonin on the hypoxia resistance and the underlying mechanisms were discovered. MTT assay revealed that hypoxia increased maximal 1.71-, 2.08-, and 2.15-fold of IC50 toward paclitaxel, ADM, and DDP in human colon cancer cell lines HCT116, respectively. Furthermore, Wogonin showed strong reversal potency in HCT116 cells in hypoxia and the RF reached 2.05. hypoxia-inducible factor-1α (HIF-1α) can activate the expression of target genes involved in glycolysis. Wogonin decreased the expression of glycolysis-related proteins (HKII, PDHK1, LDHA), glucose uptake, and lactate generation in a dose-dependent manner. Further, Western blot experiments exhibited that Wogonin could down regulate HIF-1α expression and glycolysis through inhibiting PI3K/Akt signaling pathway, which might be the mechanism of reversal resistance of Wogonin. Also, Wogonin could inhibit the growth of transplantable tumors and the expression of HIF-1α, glycolysis-related proteins and PI3K/Akt in vivo. In summary, Wogonin could be a good candidate for the development of new multidrug resistance (MDR) reversal agent and its reversal mechanism probably is due to the suppression of HIF-1α expression via inhibiting PI3K/Akt signaling pathway.
Yong Yang - One of the best experts on this subject based on the ideXlab platform.
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Wogonin induced calreticulin annexin a1 exposure dictates the immunogenicity of cancer cells in a perk akt dependent manner
PLOS ONE, 2012Co-Authors: Yong Yang, Qinglong Guo, Lei Qiang, Zhen Chen, Xuanxuan Zhu, Jing Wang, Linbo Zhang, Qidong YouAbstract:In response to ionizing irradiation and certain chemotherapeutic agents, dying tumor cells elicit a potent anticancer immune response. However, the potential effect of Wogonin (5,7-dihydroxy-8-methoxyflavone) on cancer immunogenicity has not been studied. Here we demonstrated for the first time that Wogonin elicits a potent antitumor immunity effect by inducing the translocation of calreticulin (CRT) and Annexin A1 to cell plasma membrane as well as the release of high-mobility group protein 1 (HMGB1) and ATP. Signal pathways involved in this process were studied. We found that Wogonin-induced reactive oxygen species (ROS) production causes an endoplasmic reticulum (ER) stress response, including the phosphorylation of PERK (PKR-like endoplasmic reticulum kinase)/PKR (protein kinase R) and eIF2α (eukaryotic initiation factor 2α), which served as upstream signal for the activation of phosphoinositide 3-kinase (PI3K)/AKT, inducing calreticulin (CRT)/Annexin A1 cell membrane translocation. P22/CHP, a Ca2+-binding protein, was associated with CRT and was required for CRT translocation to cell membrane. The releases of HMGB1 and ATP from Wogonin treated MFC cells, alone or together with other possible factors, activated dendritic cells and induced cytokine releases. In vivo study confirmed that immunization with Wogonin-pretreated tumor cells vaccination significantly inhibited homoplastic grafted gastric tumor growth in mice and a possible inflammatory response was involved. In conclusion, the activation of PI3K pathway elicited by ER stress induced CRT/Annexin A1 translocation (“eat me” signal) and HMGB1 release, mediating Wogonin-induced immunity of tumor cell vaccine. This indicated that Wogonin is a novel effective candidate of immunotherapy against gastric tumor.
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Wogonin induced differentiation and g1 phase arrest of human u 937 leukemia cells via pkcdelta phosphorylation
European Journal of Pharmacology, 2008Co-Authors: Haiwei Zhang, Qidong You, Kun Zhang, Yong Yang, Li Yang, Xiaotang Wang, Lan Yang, Lei Qiang, Qinglong GuoAbstract:Wogonin, a natural monoflavonoid, has been shown to have tumor therapeutic potential in vitro and in vivo. Recently many studies have focused on the induction of apoptosis of tumor cells by Wogonin. In this study, we found that Wogonin could induce differentiation and G1 phase arrest of human U-937 leukemia cells. The growth of U-937 cells incubated with Wogonin was inhibited in a time- and concentration-dependent manner. After treatment with Wogonin, U-937 cells exhibited the characteristics of mature granulocytes, such as increased cytoplasmic-to-nuclear ratio, enhanced prominence of cytoplasmic granules, membrane ruffling, a higher NBT-reducing ability, and an increased expression of CD11b. Moreover, Wogonin could induce G1 phase arrest and influenced the expression of associated proteins. For example, the expression of phorsphorylated protein kinase C (PKC) delta, p21 increased, while that of cyclin D1/cyclin-dependent kinase (CDK) 4, p-Rb decreased. The upregulation of p21 could be reversed by rottlerin, an inhibitor of PKCdelta. Taken together, Wogonin induced U-937 cells to undergo granulocytic differentiation and G1 phase arrest via PKCdelta phosphorylation-induced upregulation of p21 proteins.
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Wogonin suppresses tumor growth in vivo and vegf induced angiogenesis through inhibiting tyrosine phosphorylation of vegfr2
Life Sciences, 2008Co-Authors: Ying Gao, Qidong You, Yong Yang, Wei Liu, Xiaotang Wang, Yun Ling, Yan Chen, Qinglong GuoAbstract:Previous studies revealed that Wogonin, a naturally occurring monoflavonoid extracted from Scutellariae radix, possessed anticancer activity both in vitro and in vivo. However, the molecular mechanism of its potent anticancer activity remains poorly understood and warrants further investigations. In this study, we found for the first time that Wogonin inhibited the growth and tumor angiogenesis of human gastric carcinoma in nude mice. We explored the inhibitory effect of Wogonin on angiogenesis stimulated by vascular endothelial growth factor (VEGF) in vitro. Wogonin suppressed the VEGF-stimulated migration and tube formation of human umbilical vein endothelial cells (HUVECs). It also restrained VEGF-induced tyrosine phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2). This inhibition of receptor phosphorylation was correlated with a significant decrease in VEGF-triggered phosphorylated forms of ERK, AKT and p38. Taken together, these findings strongly suggest that Wogonin might be a promising antitumor drug.
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Wogonin induces the granulocytic differentiation of human nb4 promyelocytic leukemia cells and up regulates phospholipid scramblase 1 gene expression
Cancer Science, 2008Co-Authors: Kun Zhang, Qinglong Guo, Qidong You, Yong Yang, Haiwei Zhang, Li Yang, Zi Tan, Xiaotang WangAbstract:Previous studies have firmly demonstrated that Wogonin, a naturally occurring monoflavonoid extracted from the root of the Chinese herb medicine Scutellaria baicalensis, could effectively inhibit the proliferation of several cancer cell lines. However, little is known about the effect of Wogonin on differentiation induction of leukemic cells. Here we investigate the potential role of Wogonin in the proliferation and differentiation of NB4, a human promyelocytic leukemia cell line derived from a patient with acute promyelocytic leukemia. Our results indicated that Wogonin significantly suppressed the proliferation and efficiently induced the differentiation of NB4 cells. NB4 cell growth was inhibited by 55-60% after treatment with 50 microM Wogonin for a period of 5 days. The results of the nitroblue tetrazolium (NBT) reduction test (with 67.13% positive cells by 50 microM Wogonin for 5 days), Giemsa staining (with 67.24% positive cells by 50 microM Wogonin for 5 days), and the expression of mature-related cell-surface differentiation antigens CD11b and CD14 (with 70.94% CD11b(+) and 5.82% CD14(+) cells by 50 microM Wogonin for 5 days) demonstrated an increase in the differentiation-inducing action of Wogonin on the NB4 cells, which was accompanied by an increase in mRNA and protein expression of phospholipids scramblase 1 (PLSCR1). Meanwhile, the level of phosphorylated PKC delta (Ser643) was dramatically increased in Wogonin treated NB4 cells. Interestingly, Wogonin treatment displayed little effect on the apoptosis of NB4 cells. Taken together, the results reported here demonstrated that Wogonin could promote the granulocytic differentiation of NB4 cells by up-regulating the expression of PLSCR1 gene.
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anti hepatitis b virus activity of Wogonin in vitro and in vivo
Antiviral Research, 2007Co-Authors: Qinglong Guo, Qidong You, Yong Yang, Li Zhao, Guoliang Song, Jian XinAbstract:The traditional Chinese medicine Scutellaria radix has been used for thousands of years, mainly for the treatment of inflammatory conditions including hepatitis. The major active constituent, Wogonin (WG), isolated from S. radix has attracted increasing scientific attention in recent years due to its potent biological activities. However, pharmacologic studies have primarily been focused on Wogonin's anti-inflammatory and anti-cancer activities. In this study, we have investigated Wogonin's anti-hepatitis B virus (HBV) activity both in vitro and in vivo. In the human HBV-transfected liver cell line HepG2.2.15, Wogonin effectively suppressed the secretion of the HBV antigens with an IC(50) of 4 microg/ml at day 9 for both HBsAg and HBeAg. Consistent with the HBV antigen reduction, Wogonin also reduced HBV DNA level in a dose-dependent manner. Duck hepatitis B virus (DHBV) DNA polymerase was dramatically inhibited by Wogonin with an IC(50) of 0.57 microg/ml. In DHBV-infected ducks Wogonin dosed i.v. once a day for 10 days reduced plasma DHBV DNA level with an ED(50) of 5mg/kg. The in vivo anti-HBV effect of Wogonin in ducks was confirmed by Southern blotting of DHBV DNA in the liver. Histopathological evaluation of the liver revealed significant improvement by Wogonin. In addition, in human HBV-transgenic mice, Wogonin dosed i.v. once a day for 10 days significantly reduced plasma HBsAg level. Immunohistological staining of the liver confirmed the HBsAg reduction by Wogonin. In conclusion, our results demonstrate that Wogonin possesses potent anti-HBV activity both in vitro and in vivo. Currently, Wogonin is under early development as an anti-HBV drug candidate.
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Wogonin induces cell cycle arrest and erythroid differentiation in imatinib resistant k562 cells and primary cml cells
Oncotarget, 2014Co-Authors: Hao Yang, Qidong You, Yuxin Zhou, Kai Zhao, Xiaotang Wang, Hui Hui, Qian Wang, Yu Zhu, Qinglong GuoAbstract:// Hao Yang 1,* , Hui Hui 1,* , Qian Wang 1 , Hui Li 1 , Kai Zhao 1 , Yuxin Zhou 1 , Yu Zhu 3 , Xiaotang Wang 2 , Qidong You 1 , Qinglong Guo 1 and Na Lu 1 1 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, People’s Republic of China 2 Department of Chemistry and Biochemistry, Florida International University, Miami, FL, USA 3 Department of Hematology, The First Affiliated Hospital of Nanjing Medical University; Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu Province, People’s Republic of China * These authors contributed equally to this work Correspondence: Qing-Long Guo, email: // Na Lu, email: // Keywords : Wogonin; CML; GATA-1; differentiation; cell cycle Received : May 15, 2014 Accepted : August 09, 2014 Published : August 10, 2014 Abstract Wogonin, a flavonoid derived from Scutellaria baicalensis Georgi, has been demonstrated to be highly effective in treating hematologic malignancies. In this study, we investigated the anticancer effects of Wogonin on K562 cells, K562 imatinib-resistant cells, and primary patient-derived CML cells. Wogonin up-regulated transcription factor GATA-1 and enhanced binding between GATA-1 and FOG-1, thereby increasing expression of erythroid-differentiation genes. Wogonin also up-regulated the expression of p21 and induced cell cycle arrest. Studies employing benzidine staining and analyses of cell surface markers glycophorin A (GPA) and CD71 indicated that Wogonin promoted differentiation of K562, imatinib-resistant K562, and primary patient-derived CML cells. Wogonin also enhanced binding between GATA-1 and MEK, resulting in inhibition of the growth of CML cells. Additionally, in vivo studies showed that Wogonin decreased the number of CML cells and prolonged survival of NOD/SCID mice injected with K562 and imatinib-resistant K562 cells. These data suggested that Wogonin induces cycle arrest and erythroid differentiation in vitro and inhibits proliferation in vivo .
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Wogonin induced differentiation and g1 phase arrest of human u 937 leukemia cells via pkcdelta phosphorylation
European Journal of Pharmacology, 2008Co-Authors: Haiwei Zhang, Qidong You, Kun Zhang, Yong Yang, Li Yang, Xiaotang Wang, Lan Yang, Lei Qiang, Qinglong GuoAbstract:Wogonin, a natural monoflavonoid, has been shown to have tumor therapeutic potential in vitro and in vivo. Recently many studies have focused on the induction of apoptosis of tumor cells by Wogonin. In this study, we found that Wogonin could induce differentiation and G1 phase arrest of human U-937 leukemia cells. The growth of U-937 cells incubated with Wogonin was inhibited in a time- and concentration-dependent manner. After treatment with Wogonin, U-937 cells exhibited the characteristics of mature granulocytes, such as increased cytoplasmic-to-nuclear ratio, enhanced prominence of cytoplasmic granules, membrane ruffling, a higher NBT-reducing ability, and an increased expression of CD11b. Moreover, Wogonin could induce G1 phase arrest and influenced the expression of associated proteins. For example, the expression of phorsphorylated protein kinase C (PKC) delta, p21 increased, while that of cyclin D1/cyclin-dependent kinase (CDK) 4, p-Rb decreased. The upregulation of p21 could be reversed by rottlerin, an inhibitor of PKCdelta. Taken together, Wogonin induced U-937 cells to undergo granulocytic differentiation and G1 phase arrest via PKCdelta phosphorylation-induced upregulation of p21 proteins.
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Wogonin suppresses tumor growth in vivo and vegf induced angiogenesis through inhibiting tyrosine phosphorylation of vegfr2
Life Sciences, 2008Co-Authors: Ying Gao, Qidong You, Yong Yang, Wei Liu, Xiaotang Wang, Yun Ling, Yan Chen, Qinglong GuoAbstract:Previous studies revealed that Wogonin, a naturally occurring monoflavonoid extracted from Scutellariae radix, possessed anticancer activity both in vitro and in vivo. However, the molecular mechanism of its potent anticancer activity remains poorly understood and warrants further investigations. In this study, we found for the first time that Wogonin inhibited the growth and tumor angiogenesis of human gastric carcinoma in nude mice. We explored the inhibitory effect of Wogonin on angiogenesis stimulated by vascular endothelial growth factor (VEGF) in vitro. Wogonin suppressed the VEGF-stimulated migration and tube formation of human umbilical vein endothelial cells (HUVECs). It also restrained VEGF-induced tyrosine phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2). This inhibition of receptor phosphorylation was correlated with a significant decrease in VEGF-triggered phosphorylated forms of ERK, AKT and p38. Taken together, these findings strongly suggest that Wogonin might be a promising antitumor drug.
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Wogonin induces the granulocytic differentiation of human nb4 promyelocytic leukemia cells and up regulates phospholipid scramblase 1 gene expression
Cancer Science, 2008Co-Authors: Kun Zhang, Qinglong Guo, Qidong You, Yong Yang, Haiwei Zhang, Li Yang, Zi Tan, Xiaotang WangAbstract:Previous studies have firmly demonstrated that Wogonin, a naturally occurring monoflavonoid extracted from the root of the Chinese herb medicine Scutellaria baicalensis, could effectively inhibit the proliferation of several cancer cell lines. However, little is known about the effect of Wogonin on differentiation induction of leukemic cells. Here we investigate the potential role of Wogonin in the proliferation and differentiation of NB4, a human promyelocytic leukemia cell line derived from a patient with acute promyelocytic leukemia. Our results indicated that Wogonin significantly suppressed the proliferation and efficiently induced the differentiation of NB4 cells. NB4 cell growth was inhibited by 55-60% after treatment with 50 microM Wogonin for a period of 5 days. The results of the nitroblue tetrazolium (NBT) reduction test (with 67.13% positive cells by 50 microM Wogonin for 5 days), Giemsa staining (with 67.24% positive cells by 50 microM Wogonin for 5 days), and the expression of mature-related cell-surface differentiation antigens CD11b and CD14 (with 70.94% CD11b(+) and 5.82% CD14(+) cells by 50 microM Wogonin for 5 days) demonstrated an increase in the differentiation-inducing action of Wogonin on the NB4 cells, which was accompanied by an increase in mRNA and protein expression of phospholipids scramblase 1 (PLSCR1). Meanwhile, the level of phosphorylated PKC delta (Ser643) was dramatically increased in Wogonin treated NB4 cells. Interestingly, Wogonin treatment displayed little effect on the apoptosis of NB4 cells. Taken together, the results reported here demonstrated that Wogonin could promote the granulocytic differentiation of NB4 cells by up-regulating the expression of PLSCR1 gene.
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involvement of bax bcl 2 in Wogonin induced apoptosis of human hepatoma cell line smmc 7721
Anti-Cancer Drugs, 2006Co-Authors: Wei Wang, Qinglong Guo, Qidong You, Kun Zhang, Yong Yang, Wei Liu, Li Zhao, Zi Tan, Xiaotang WangAbstract:The molecular mechanisms of Wogonin-induced apoptosis of human hepatoma SMMC-7721 cells are reported. Wogonin treatment resulted in significant inhibition of SMMC-7721 cells in a time-dependent and concentration-dependent manner. Typical morphological changes and apoptotic blebbing in SMMC-7721 cell
