The Experts below are selected from a list of 774 Experts worldwide ranked by ideXlab platform
Hye Gwang Jeong - One of the best experts on this subject based on the ideXlab platform.
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suppression of pma induced human fibrosarcoma ht 1080 invasion and metastasis by Kahweol via inhibiting akt jnk1 2 p38 mapk signal pathway and nf κb dependent transcriptional activities
Food and Chemical Toxicology, 2019Co-Authors: Jae Ho Choi, Yong Pil Hwang, Young Chul Chung, Keon Wook Kang, Hye Gwang JeongAbstract:Abstract Coffee is one of the widely sales beverage worldwide and contains numerous phytochemicals that are beneficial to health. Kahweol acetate (KA), a coffee-specific diterpene, exhibits anti-tumoric properties in human tumoric cells. However, the effect of KA on the metastasis and invasion of cancer cells and the underlying mechanisms remain unclear. The objectives of this study were to estimate the anti-tumor activity of KA and reveal the possible molecular mechanisms. KA markedly inhibited the cell proliferation enhanced by phorbol 12-myristate 13-acetate (PMA) in human fibrosarcoma cells. As well as, KA attenuated PMA-induced cell migration and invasion in a concentration-dependent manner. KA suppressed PMA-enhanced activation of matrix metalloproteinase-9 (MMP-9) through suppression of nuclear factor kappa B (NF-κB) activation. KA repressed the PMA-induced phosphorylation of Akt, c-Jun N-terminal kinase (JNK) 1/2, and p38 MAPK, which are signaling molecules upstream of MMP-9 expression. In summary, we demonstrated that the anti-tumor effects of KA might occur through the inhibition of Akt/JNK1/2/p38 MAPK phosphorylation and downregulation of NF-κB activation, leading to a decrease in MMP-9 expression. Thus, KA is a useful chemotherapeutic agent that may contribute to prevent to the metastatic tumor.
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Suppression of PMA-induced human fibrosarcoma HT-1080 invasion and metastasis by Kahweol via inhibiting Akt/JNK1/2/p38 MAPK signal pathway and NF-κB dependent transcriptional activities.
Food and Chemical Toxicology, 2018Co-Authors: Jae Ho Choi, Yong Pil Hwang, Young Chul Chung, Keon Wook Kang, Hye Gwang JeongAbstract:Abstract Coffee is one of the widely sales beverage worldwide and contains numerous phytochemicals that are beneficial to health. Kahweol acetate (KA), a coffee-specific diterpene, exhibits anti-tumoric properties in human tumoric cells. However, the effect of KA on the metastasis and invasion of cancer cells and the underlying mechanisms remain unclear. The objectives of this study were to estimate the anti-tumor activity of KA and reveal the possible molecular mechanisms. KA markedly inhibited the cell proliferation enhanced by phorbol 12-myristate 13-acetate (PMA) in human fibrosarcoma cells. As well as, KA attenuated PMA-induced cell migration and invasion in a concentration-dependent manner. KA suppressed PMA-enhanced activation of matrix metalloproteinase-9 (MMP-9) through suppression of nuclear factor kappa B (NF-κB) activation. KA repressed the PMA-induced phosphorylation of Akt, c-Jun N-terminal kinase (JNK) 1/2, and p38 MAPK, which are signaling molecules upstream of MMP-9 expression. In summary, we demonstrated that the anti-tumor effects of KA might occur through the inhibition of Akt/JNK1/2/p38 MAPK phosphorylation and downregulation of NF-κB activation, leading to a decrease in MMP-9 expression. Thus, KA is a useful chemotherapeutic agent that may contribute to prevent to the metastatic tumor.
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Kahweol inhibits proliferation and induces apoptosis by suppressing fatty acid synthase in her2 overexpressing cancer cells
Food and Chemical Toxicology, 2018Co-Authors: Suck Hoon Oh, Yong Pil Hwang, Jae Ho Choi, Young Ho Chung, Young Chul Chung, Hye Gwang JeongAbstract:Abstract Kahweol is a coffee-specific diterpene found in the beans of Coffea arabica and has been reported to demonstrate various biological activities, including anti-inflammatory, antioxidant, and apoptotic properties. In the present study, we examined the molecular mechanism of Kahweol in human epidermal growth factor receptor-2 (HER2)-overexpressing breast cancer cells. Kahweol preferentially inhibited cell proliferation and induced cell death through the induction of a caspase 3-dependent pathway in HER2-overexpression breast cancer cell lines. Kahweol treatment substantially reduced the levels of HER2 protein, mRNA, and transcriptional activity in SKBR3 cells. Kahweol exerts its potent anticancer efficacy by the upregulation of polyomavirus enhancer activator 3 (PEA3) and downregulation of activator protein 2 (AP-2) to inhibit aberrantly activated HER2 signaling. Fatty acid synthase (FASN) expression and sterol regulatory element-binding protein-1c (SREBP-1c) activity were downregulated by Kahweol. In addition, Kahweol lowered the levels of phosphorylated Akt and its downstream targets mammalian target of rapamycin (mTOR) and cyclin D1. Furthermore, we found that blocking Akt signaling through Kahweol treatment significantly reduced FASN expression and subsequently suppressed cell proliferation in HER2-overexpressing cancer cells. Overall, this study suggests that Kahweol could be a useful adjuvant therapeutic agent in the treatment of HER2-overexpressing breast cancer.
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the coffee diterpene Kahweol inhibits metastasis by modulating expressions of mmps and vegf via stat3 inactivation
Food Chemistry, 2012Co-Authors: Yong Pil Hwang, Jae Ho Choi, Young Chul Chung, Kwangil Kwon, Myung Ho Jeong, Tae Cheon Jeong, Wonku Kang, Hye Gwang JeongAbstract:Kahweol, a coffee-specific diterpene, is reported to have anti-cancer properties, although its precise chemopreventive mechanism remains unclear. The aim of our study was to determine the effect of Kahweol on anti-metastatic activities and the possible mechanisms. Kahweol inhibited the migration and invasion ability of various cancer cells in vitro and decreased the secretion of metalloproteinase (MMP)-2, MMP-9, and VEGF in cancer cells via suppression of STAT3 activation. Kahweol also exhibited an inhibitory effect on lung metastasis in the experimental B16-F10 melanoma metastasis model. Moreover, Kahweol inhibited migration and tube formation of endothelial cells in vitro, decreased the secretion of VEGF, and suppressed neovascularisation in Matrigel plugs in mice. Our findings demonstrate that Kahweol inhibits metastasis through the disruption of STAT3-mediated transcription of the MMP and VEGF genes.
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Kahweol blocks stat3 phosphorylation and induces apoptosis in human lung adenocarcinoma a549 cells
Toxicology Letters, 2009Co-Authors: Yong Pil Hwang, Hye Gwang JeongAbstract:Abstract Kahweol, the coffee-specific diterpene, has been reported to have anti-carcinogenic properties. Animal data support such a chemopreventive effect of coffee. However, the precise underlying protective mechanisms are poorly understood. In this study, the apoptotic effect of Kahweol in human lung adenocarcinoma A549 cells was investigated. In cell viability assays and cell proliferation assays, Kahweol exhibited anti-proliferative and pro-apoptotic effects on A549 cells in a time- and dose-dependent manner. Kahweol considerably inhibited the expression of Bcl-2 but increased that of Bax; it also stimulated the cleavage of caspase-3 and PARP (poly ADP-ribose polymerase). In addition, Kahweol-induced apoptosis was confirmed by TUNEL assays. Furthermore, Kahweol inhibited dose-dependent phosphorylation of signal transducer and activator of transcription 3 (STAT3). An overexpression in STAT3 led to resistance to Kahweol-induced apoptosis, suggesting that STAT3 was a critical target of Kahweol. These findings suggest that Kahweol inhibited A549 cell growth and induced apoptosis via down-regulation of STAT3 signaling pathway.
Taeg Kyu Kwon - One of the best experts on this subject based on the ideXlab platform.
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Kahweol inhibits adipogenesis of 3t3 l1 adipocytes through downregulation of pparγ
Natural Product Research, 2018Co-Authors: Young Jin Kang, Taeg Kyu KwonAbstract:Kahweol, a compound from Coffea arabica, possesses antioxidant, anti-inflammatory, and antitumour properties. However, an anti-adipogenic effect has not yet been reported. In this study, we have shown that Kahweol has an anti-adipogenic effect on 3T3-L1 adipocytes. Kahweol significantly inhibited the differentiation of intracellular lipid accumulation in 3T3-L1 adipocytes, without being cytotoxic. It also downregulated the expression of adipogenesis-related gene, including an adipocytokine, adiponectin. This anti-adipogenic effect stems from an ability to inhibit key adipogenic regulators, including PPARγ and C/EBPα. These results demonstrate that Kahweol significantly inhibits the differentiation of 3T3-L1 cells, and suggest that it has potential as a novel anti-obesity treatment.
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the coffee diterpene Kahweol enhances sensitivity to sorafenib in human renal carcinoma caki cells through down regulation of mcl 1 and c flip expression
Oncotarget, 2017Co-Authors: Hee Jung Um, Taeg Kyu KwonAbstract:// Kyoung-Jin Min 1 , Hee Jung Um 1 , Jee In Kim 2 and Taeg Kyu Kwon 1 1 Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701, South Korea 2 Department of Molecular Medicine, School of Medicine, Keimyung University, Daegu 704-701, South Korea Correspondence to: Taeg Kyu Kwon, email: kwontk@dsmc.or.kr Keywords: sorafenib, Kahweol, Mcl-1, c-FLIP Received: June 21, 2017 Accepted: July 30, 2017 Published: August 24, 2017 ABSTRACT Sorafenib is approved for the treatment of hepatocellular carcinoma (HCC) and advanced renal cell carcinoma (RCC). However, low tumor response and side effects have been widely reported. Therefore, to improve the efficacy of sorafenib, we investigated whether combined treatment with sorafenib and Kahweol, the coffee-specific diterpene, has a synergistic effect on apoptotic cell death. Combined treatment with sorafenib and Kahweol markedly induced caspase-mediated apoptosis in renal carcinoma Caki cells. Combined treatment with sorafenib and Kahweol induced down-regulation of Mcl-1 and c-FLIP expression. We found down-regulation of Mcl-1 and c-FLIP expression was modulated by the ubiquitin-proteasome pathway. Ectopic expression of Mcl-1 inhibited sorafenib plus Kahweol-induced apoptosis. Interestingly, combined treatment with sorafenib and Kahweol induced apoptotic cell death in c-FLIP overexpressed cells. In addition, combined treatment with sorafenib and Kahweol markedly induced apoptosis in human lung carcinoma (A549) and breast carcinoma (MDA-MB-361) cells, but not in human normal mesangial cells and human skin fibroblast cells (HSF). Collectively, our study demonstrates that combined treatment with sorafenib and Kahweol induces apoptotic cell death through down-regulation of Mcl-1 expression.
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melatonin sensitizes caki renal cancer cells to Kahweol induced apoptosis through chop mediated up regulation of puma
Journal of Pineal Research, 2011Co-Authors: Hee Jung Um, Jongwook Park, Taeg Kyu KwonAbstract:Melatonin has recently gained attention as a regulator of biologic processes in addition to its effects on circadian rhythms. The mechanisms whereby melatonin regulates the apoptotic program remain poorly understood. In this study, we investigated the combined effect of melatonin and Kahweol on apoptosis of cancer cells, but not in most normal human cell types, thus presenting an attractive novel strategy for cancer treatment. In our experiments, treatment with a combination of melatonin and Kahweol induced apoptosis, stimulated DEVDase activity, and DNA fragmentation. Co-treatment with melatonin and Kahweol induced up-regulation of p53-upregulated modulator of apoptosis (PUMA) while down-regulation of PUMA expression using small interfering RNAs attenuated melatonin plus Kahweol-induced apoptosis. In addition, co-treatment with Kahweol and melatonin induced PUMA up-regulation through endoplasmic reticulum stress-mediated C/EBP homologous protein induction and the p53-independent pathway. Our results collectively demonstrate that up-regulation of PUMA contributes to the sensitizing effect of melatonin plus Kahweol on apoptosis in cancer cells.
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Melatonin sensitizes Caki renal cancer cells to Kahweol‐induced apoptosis through CHOP‐mediated up‐regulation of PUMA
Journal of Pineal Research, 2011Co-Authors: Hee Jung Um, Jongwook Park, Taeg Kyu KwonAbstract:Melatonin has recently gained attention as a regulator of biologic processes in addition to its effects on circadian rhythms. The mechanisms whereby melatonin regulates the apoptotic program remain poorly understood. In this study, we investigated the combined effect of melatonin and Kahweol on apoptosis of cancer cells, but not in most normal human cell types, thus presenting an attractive novel strategy for cancer treatment. In our experiments, treatment with a combination of melatonin and Kahweol induced apoptosis, stimulated DEVDase activity, and DNA fragmentation. Co-treatment with melatonin and Kahweol induced up-regulation of p53-upregulated modulator of apoptosis (PUMA) while down-regulation of PUMA expression using small interfering RNAs attenuated melatonin plus Kahweol-induced apoptosis. In addition, co-treatment with Kahweol and melatonin induced PUMA up-regulation through endoplasmic reticulum stress-mediated C/EBP homologous protein induction and the p53-independent pathway. Our results collectively demonstrate that up-regulation of PUMA contributes to the sensitizing effect of melatonin plus Kahweol on apoptosis in cancer cells.
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the coffee diterpene Kahweol sensitizes trail induced apoptosis in renal carcinoma caki cells through down regulation of bcl 2 and c flip
Chemico-Biological Interactions, 2010Co-Authors: Hee Jung Um, Jung Hwa Oh, Yung Hyun Choi, Jongwook Park, Taeg Kyu KwonAbstract:Abstract Kahweol, a coffee-specific diterpene, found in the beans of Coffea arabica, has potent anti-carcinogenic, anti-tumor, and anti-inflammatory properties. TRAIL is a potential anti-cancer compound that induces apoptosis in a wide variety of cancer cells, but not in most normal human cell types. In the present study, we show that Kahweol sensitizes human renal cancer cells, but not normal human mesangial cells, to TRAIL-mediated apoptosis. Moreover, treatment with a combination of Kahweol and TRAIL induces significant apoptosis in various cancer cell types, thus presenting an attractive novel strategy for cancer treatment. Our experiments show that treatment with a combination of Kahweol and TRAIL-induced apoptosis, and stimulated of DEVDase activity, DNA fragmentation, and cleavage of PARP, which was prevented by pretreatment with z-VAD, indicative of cell death via a caspase-dependent pathway. Kahweol-induced down-regulation of Bcl-2 and ectopic expression of Bcl-2 led to attenuation of Kahweol plus TRAIL-mediated apoptosis, indicative of Bcl-2 involvement in the apoptotic process. In addition, the c-FLIP and caspase signal pathways seem to play a crucial role in apoptosis triggered by the combination of Kahweol and TRAIL in Caki cells. Our results collectively demonstrate that down-regulation of Bcl-2 and c-FLIP contributes to the sensitizing effect of Kahweol on TRAIL-mediated apoptosis in cancer cells.
Yong Pil Hwang - One of the best experts on this subject based on the ideXlab platform.
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suppression of pma induced human fibrosarcoma ht 1080 invasion and metastasis by Kahweol via inhibiting akt jnk1 2 p38 mapk signal pathway and nf κb dependent transcriptional activities
Food and Chemical Toxicology, 2019Co-Authors: Jae Ho Choi, Yong Pil Hwang, Young Chul Chung, Keon Wook Kang, Hye Gwang JeongAbstract:Abstract Coffee is one of the widely sales beverage worldwide and contains numerous phytochemicals that are beneficial to health. Kahweol acetate (KA), a coffee-specific diterpene, exhibits anti-tumoric properties in human tumoric cells. However, the effect of KA on the metastasis and invasion of cancer cells and the underlying mechanisms remain unclear. The objectives of this study were to estimate the anti-tumor activity of KA and reveal the possible molecular mechanisms. KA markedly inhibited the cell proliferation enhanced by phorbol 12-myristate 13-acetate (PMA) in human fibrosarcoma cells. As well as, KA attenuated PMA-induced cell migration and invasion in a concentration-dependent manner. KA suppressed PMA-enhanced activation of matrix metalloproteinase-9 (MMP-9) through suppression of nuclear factor kappa B (NF-κB) activation. KA repressed the PMA-induced phosphorylation of Akt, c-Jun N-terminal kinase (JNK) 1/2, and p38 MAPK, which are signaling molecules upstream of MMP-9 expression. In summary, we demonstrated that the anti-tumor effects of KA might occur through the inhibition of Akt/JNK1/2/p38 MAPK phosphorylation and downregulation of NF-κB activation, leading to a decrease in MMP-9 expression. Thus, KA is a useful chemotherapeutic agent that may contribute to prevent to the metastatic tumor.
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Suppression of PMA-induced human fibrosarcoma HT-1080 invasion and metastasis by Kahweol via inhibiting Akt/JNK1/2/p38 MAPK signal pathway and NF-κB dependent transcriptional activities.
Food and Chemical Toxicology, 2018Co-Authors: Jae Ho Choi, Yong Pil Hwang, Young Chul Chung, Keon Wook Kang, Hye Gwang JeongAbstract:Abstract Coffee is one of the widely sales beverage worldwide and contains numerous phytochemicals that are beneficial to health. Kahweol acetate (KA), a coffee-specific diterpene, exhibits anti-tumoric properties in human tumoric cells. However, the effect of KA on the metastasis and invasion of cancer cells and the underlying mechanisms remain unclear. The objectives of this study were to estimate the anti-tumor activity of KA and reveal the possible molecular mechanisms. KA markedly inhibited the cell proliferation enhanced by phorbol 12-myristate 13-acetate (PMA) in human fibrosarcoma cells. As well as, KA attenuated PMA-induced cell migration and invasion in a concentration-dependent manner. KA suppressed PMA-enhanced activation of matrix metalloproteinase-9 (MMP-9) through suppression of nuclear factor kappa B (NF-κB) activation. KA repressed the PMA-induced phosphorylation of Akt, c-Jun N-terminal kinase (JNK) 1/2, and p38 MAPK, which are signaling molecules upstream of MMP-9 expression. In summary, we demonstrated that the anti-tumor effects of KA might occur through the inhibition of Akt/JNK1/2/p38 MAPK phosphorylation and downregulation of NF-κB activation, leading to a decrease in MMP-9 expression. Thus, KA is a useful chemotherapeutic agent that may contribute to prevent to the metastatic tumor.
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Kahweol inhibits proliferation and induces apoptosis by suppressing fatty acid synthase in her2 overexpressing cancer cells
Food and Chemical Toxicology, 2018Co-Authors: Suck Hoon Oh, Yong Pil Hwang, Jae Ho Choi, Young Ho Chung, Young Chul Chung, Hye Gwang JeongAbstract:Abstract Kahweol is a coffee-specific diterpene found in the beans of Coffea arabica and has been reported to demonstrate various biological activities, including anti-inflammatory, antioxidant, and apoptotic properties. In the present study, we examined the molecular mechanism of Kahweol in human epidermal growth factor receptor-2 (HER2)-overexpressing breast cancer cells. Kahweol preferentially inhibited cell proliferation and induced cell death through the induction of a caspase 3-dependent pathway in HER2-overexpression breast cancer cell lines. Kahweol treatment substantially reduced the levels of HER2 protein, mRNA, and transcriptional activity in SKBR3 cells. Kahweol exerts its potent anticancer efficacy by the upregulation of polyomavirus enhancer activator 3 (PEA3) and downregulation of activator protein 2 (AP-2) to inhibit aberrantly activated HER2 signaling. Fatty acid synthase (FASN) expression and sterol regulatory element-binding protein-1c (SREBP-1c) activity were downregulated by Kahweol. In addition, Kahweol lowered the levels of phosphorylated Akt and its downstream targets mammalian target of rapamycin (mTOR) and cyclin D1. Furthermore, we found that blocking Akt signaling through Kahweol treatment significantly reduced FASN expression and subsequently suppressed cell proliferation in HER2-overexpressing cancer cells. Overall, this study suggests that Kahweol could be a useful adjuvant therapeutic agent in the treatment of HER2-overexpressing breast cancer.
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the coffee diterpene Kahweol inhibits metastasis by modulating expressions of mmps and vegf via stat3 inactivation
Food Chemistry, 2012Co-Authors: Yong Pil Hwang, Jae Ho Choi, Young Chul Chung, Kwangil Kwon, Myung Ho Jeong, Tae Cheon Jeong, Wonku Kang, Hye Gwang JeongAbstract:Kahweol, a coffee-specific diterpene, is reported to have anti-cancer properties, although its precise chemopreventive mechanism remains unclear. The aim of our study was to determine the effect of Kahweol on anti-metastatic activities and the possible mechanisms. Kahweol inhibited the migration and invasion ability of various cancer cells in vitro and decreased the secretion of metalloproteinase (MMP)-2, MMP-9, and VEGF in cancer cells via suppression of STAT3 activation. Kahweol also exhibited an inhibitory effect on lung metastasis in the experimental B16-F10 melanoma metastasis model. Moreover, Kahweol inhibited migration and tube formation of endothelial cells in vitro, decreased the secretion of VEGF, and suppressed neovascularisation in Matrigel plugs in mice. Our findings demonstrate that Kahweol inhibits metastasis through the disruption of STAT3-mediated transcription of the MMP and VEGF genes.
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Kahweol blocks stat3 phosphorylation and induces apoptosis in human lung adenocarcinoma a549 cells
Toxicology Letters, 2009Co-Authors: Yong Pil Hwang, Hye Gwang JeongAbstract:Abstract Kahweol, the coffee-specific diterpene, has been reported to have anti-carcinogenic properties. Animal data support such a chemopreventive effect of coffee. However, the precise underlying protective mechanisms are poorly understood. In this study, the apoptotic effect of Kahweol in human lung adenocarcinoma A549 cells was investigated. In cell viability assays and cell proliferation assays, Kahweol exhibited anti-proliferative and pro-apoptotic effects on A549 cells in a time- and dose-dependent manner. Kahweol considerably inhibited the expression of Bcl-2 but increased that of Bax; it also stimulated the cleavage of caspase-3 and PARP (poly ADP-ribose polymerase). In addition, Kahweol-induced apoptosis was confirmed by TUNEL assays. Furthermore, Kahweol inhibited dose-dependent phosphorylation of signal transducer and activator of transcription 3 (STAT3). An overexpression in STAT3 led to resistance to Kahweol-induced apoptosis, suggesting that STAT3 was a critical target of Kahweol. These findings suggest that Kahweol inhibited A549 cell growth and induced apoptosis via down-regulation of STAT3 signaling pathway.
Hee Jung Um - One of the best experts on this subject based on the ideXlab platform.
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the coffee diterpene Kahweol enhances sensitivity to sorafenib in human renal carcinoma caki cells through down regulation of mcl 1 and c flip expression
Oncotarget, 2017Co-Authors: Hee Jung Um, Taeg Kyu KwonAbstract:// Kyoung-Jin Min 1 , Hee Jung Um 1 , Jee In Kim 2 and Taeg Kyu Kwon 1 1 Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701, South Korea 2 Department of Molecular Medicine, School of Medicine, Keimyung University, Daegu 704-701, South Korea Correspondence to: Taeg Kyu Kwon, email: kwontk@dsmc.or.kr Keywords: sorafenib, Kahweol, Mcl-1, c-FLIP Received: June 21, 2017 Accepted: July 30, 2017 Published: August 24, 2017 ABSTRACT Sorafenib is approved for the treatment of hepatocellular carcinoma (HCC) and advanced renal cell carcinoma (RCC). However, low tumor response and side effects have been widely reported. Therefore, to improve the efficacy of sorafenib, we investigated whether combined treatment with sorafenib and Kahweol, the coffee-specific diterpene, has a synergistic effect on apoptotic cell death. Combined treatment with sorafenib and Kahweol markedly induced caspase-mediated apoptosis in renal carcinoma Caki cells. Combined treatment with sorafenib and Kahweol induced down-regulation of Mcl-1 and c-FLIP expression. We found down-regulation of Mcl-1 and c-FLIP expression was modulated by the ubiquitin-proteasome pathway. Ectopic expression of Mcl-1 inhibited sorafenib plus Kahweol-induced apoptosis. Interestingly, combined treatment with sorafenib and Kahweol induced apoptotic cell death in c-FLIP overexpressed cells. In addition, combined treatment with sorafenib and Kahweol markedly induced apoptosis in human lung carcinoma (A549) and breast carcinoma (MDA-MB-361) cells, but not in human normal mesangial cells and human skin fibroblast cells (HSF). Collectively, our study demonstrates that combined treatment with sorafenib and Kahweol induces apoptotic cell death through down-regulation of Mcl-1 expression.
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melatonin sensitizes caki renal cancer cells to Kahweol induced apoptosis through chop mediated up regulation of puma
Journal of Pineal Research, 2011Co-Authors: Hee Jung Um, Jongwook Park, Taeg Kyu KwonAbstract:Melatonin has recently gained attention as a regulator of biologic processes in addition to its effects on circadian rhythms. The mechanisms whereby melatonin regulates the apoptotic program remain poorly understood. In this study, we investigated the combined effect of melatonin and Kahweol on apoptosis of cancer cells, but not in most normal human cell types, thus presenting an attractive novel strategy for cancer treatment. In our experiments, treatment with a combination of melatonin and Kahweol induced apoptosis, stimulated DEVDase activity, and DNA fragmentation. Co-treatment with melatonin and Kahweol induced up-regulation of p53-upregulated modulator of apoptosis (PUMA) while down-regulation of PUMA expression using small interfering RNAs attenuated melatonin plus Kahweol-induced apoptosis. In addition, co-treatment with Kahweol and melatonin induced PUMA up-regulation through endoplasmic reticulum stress-mediated C/EBP homologous protein induction and the p53-independent pathway. Our results collectively demonstrate that up-regulation of PUMA contributes to the sensitizing effect of melatonin plus Kahweol on apoptosis in cancer cells.
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Melatonin sensitizes Caki renal cancer cells to Kahweol‐induced apoptosis through CHOP‐mediated up‐regulation of PUMA
Journal of Pineal Research, 2011Co-Authors: Hee Jung Um, Jongwook Park, Taeg Kyu KwonAbstract:Melatonin has recently gained attention as a regulator of biologic processes in addition to its effects on circadian rhythms. The mechanisms whereby melatonin regulates the apoptotic program remain poorly understood. In this study, we investigated the combined effect of melatonin and Kahweol on apoptosis of cancer cells, but not in most normal human cell types, thus presenting an attractive novel strategy for cancer treatment. In our experiments, treatment with a combination of melatonin and Kahweol induced apoptosis, stimulated DEVDase activity, and DNA fragmentation. Co-treatment with melatonin and Kahweol induced up-regulation of p53-upregulated modulator of apoptosis (PUMA) while down-regulation of PUMA expression using small interfering RNAs attenuated melatonin plus Kahweol-induced apoptosis. In addition, co-treatment with Kahweol and melatonin induced PUMA up-regulation through endoplasmic reticulum stress-mediated C/EBP homologous protein induction and the p53-independent pathway. Our results collectively demonstrate that up-regulation of PUMA contributes to the sensitizing effect of melatonin plus Kahweol on apoptosis in cancer cells.
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the coffee diterpene Kahweol sensitizes trail induced apoptosis in renal carcinoma caki cells through down regulation of bcl 2 and c flip
Chemico-Biological Interactions, 2010Co-Authors: Hee Jung Um, Jung Hwa Oh, Yung Hyun Choi, Jongwook Park, Taeg Kyu KwonAbstract:Abstract Kahweol, a coffee-specific diterpene, found in the beans of Coffea arabica, has potent anti-carcinogenic, anti-tumor, and anti-inflammatory properties. TRAIL is a potential anti-cancer compound that induces apoptosis in a wide variety of cancer cells, but not in most normal human cell types. In the present study, we show that Kahweol sensitizes human renal cancer cells, but not normal human mesangial cells, to TRAIL-mediated apoptosis. Moreover, treatment with a combination of Kahweol and TRAIL induces significant apoptosis in various cancer cell types, thus presenting an attractive novel strategy for cancer treatment. Our experiments show that treatment with a combination of Kahweol and TRAIL-induced apoptosis, and stimulated of DEVDase activity, DNA fragmentation, and cleavage of PARP, which was prevented by pretreatment with z-VAD, indicative of cell death via a caspase-dependent pathway. Kahweol-induced down-regulation of Bcl-2 and ectopic expression of Bcl-2 led to attenuation of Kahweol plus TRAIL-mediated apoptosis, indicative of Bcl-2 involvement in the apoptotic process. In addition, the c-FLIP and caspase signal pathways seem to play a crucial role in apoptosis triggered by the combination of Kahweol and TRAIL in Caki cells. Our results collectively demonstrate that down-regulation of Bcl-2 and c-FLIP contributes to the sensitizing effect of Kahweol on TRAIL-mediated apoptosis in cancer cells.
Jin Boo Jeong - One of the best experts on this subject based on the ideXlab platform.
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Kahweol from Coffee Induces Apoptosis by Upregulating Activating Transcription Factor 3 in Human Colorectal Cancer Cells.
Biomolecules & Therapeutics, 2017Co-Authors: Gwang Hun Park, Hun Min Song, Jin Boo JeongAbstract:Kahweol as a coffee-specific diterpene has been reported to induce apoptosis in human cancer cells. Although some molecular targets for Kahweol-mediated apoptosis have been elucidated, the further mechanism for apoptotic effect of Kahweol is not known. Activating transcription factor 3 (ATF3) has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which Kahweol stimulates ATF3 expression and apoptosis in human colorectal cancer cells. Kahweol increased apoptosis in human colorectal cancer cells. It also increased ATF3 expression through the transcriptional activity. The responsible cis-element for ATF3 transcriptional activation by Kahweol was CREB located between -147 to -85 of ATF3 promoter. ATF3 overexpression increased Kahweol-mediated cleaved PARP, while ATF3 knockdown attenuated the cleavage of PARP by Kahweol. Inhibition of ERK1/2 and GSK3β blocked Kahweol-mediated ATF3 expression. The results suggest that Kahweol induces apoptosis through ATF3-mediated pathway in human colorectal cancer cells.
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the coffee diterpene Kahweol suppresses the cell proliferation by inducing cyclin d1 proteasomal degradation via erk1 2 jnk and gks3β dependent threonine 286 phosphorylation in human colorectal cancer cells
Food and Chemical Toxicology, 2016Co-Authors: Gwang Hun Park, Hun Min Song, Jin Boo JeongAbstract:Kahweol as a coffee-specific diterpene has been reported to exert anti-cancer properties. However, the mechanism responsible for the anti-cancer effects of Kahweol is not fully understood. The main aim of this investigation was to determine the effect of Kahweol on cell proliferation and the possible mechanisms in human colorectal cancer cells. Kahweol inhibited markedly the proliferation of human colorectal cancer cell lines such as HCT116, SW480. Kahweol decreased cyclin D1 protein level in HCT116 and SW480 cells. Contrast to protein levels, cyclin D1 mRNA level and promoter activity did not be changed by Kahweol treatment. MG132 treatment attenuated Kahweol-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in Kahweol-treated cells. Kahweol increased phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine attenuated cyclin D1 degradation by Kahweol. Inhibition of ERK1/2 by PD98059, JNK by SP600125 or GSK3β by LiCl suppressed cyclin D1 phosphorylation and downregulation by Kahweol. Furthermore, the inhibition of nuclear export by LMB attenuated cyclin D1 degradation by Kahweol. In conclusion, Kahweol-mediated cyclin D1 degradation may contribute to the inhibition of the proliferation in human colorectal cancer cells.
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The coffee diterpene Kahweol suppresses the cell proliferation by inducing cyclin D1 proteasomal degradation via ERK1/2, JNK and GKS3β-dependent threonine-286 phosphorylation in human colorectal cancer cells.
Food and Chemical Toxicology, 2016Co-Authors: Gwang Hun Park, Hun Min Song, Jin Boo JeongAbstract:Kahweol as a coffee-specific diterpene has been reported to exert anti-cancer properties. However, the mechanism responsible for the anti-cancer effects of Kahweol is not fully understood. The main aim of this investigation was to determine the effect of Kahweol on cell proliferation and the possible mechanisms in human colorectal cancer cells. Kahweol inhibited markedly the proliferation of human colorectal cancer cell lines such as HCT116, SW480. Kahweol decreased cyclin D1 protein level in HCT116 and SW480 cells. Contrast to protein levels, cyclin D1 mRNA level and promoter activity did not be changed by Kahweol treatment. MG132 treatment attenuated Kahweol-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in Kahweol-treated cells. Kahweol increased phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine attenuated cyclin D1 degradation by Kahweol. Inhibition of ERK1/2 by PD98059, JNK by SP600125 or GSK3β by LiCl suppressed cyclin D1 phosphorylation and downregulation by Kahweol. Furthermore, the inhibition of nuclear export by LMB attenuated cyclin D1 degradation by Kahweol. In conclusion, Kahweol-mediated cyclin D1 degradation may contribute to the inhibition of the proliferation in human colorectal cancer cells.