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Zhaoxiang Bian - One of the best experts on this subject based on the ideXlab platform.
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halofuginone and artemisinin synergistically arrest cancer cells at the g1 G0 Phase by upregulating p21cip1 and p27kip1
Oncotarget, 2016Co-Authors: Guoqing Chen, Ruihong Gong, Xianli Shi, Dajian Yang, Ge Zhang, Jianbo Yue, Zhaoxiang BianAbstract:// Guoqing Chen 1, 2, * , Ruihong Gong 1, * , Xianli Shi 3 , Dajian Yang 2 , Ge Zhang 1 , Aiping Lu 1 , Jianbo Yue 3 , Zhaoxiang Bian 1 1 School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China 2 Chongqing Academy of Chinese Materia Medica, Chongqing, China 3 Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China * These authors have contributed equally to this work Correspondence to: Jianbo Yue, email: jianbyue@cityu.edu.hk Zhaoxiang Bian, email: bzxiang@hkbu.edu.hk Keywords: halofuginone, artemisinin, synergy, cell proliferation, cell cycle Received: February 24, 2016 Accepted: June 9, 2016 Published: July 1, 2016 ABSTRACT Combinational drug therapy is one of the most promising strategies in modern anticancer research. Traditional Chinese medicine (TCM) formulas represent a wealth of complex combinations proven successful over centuries of clinical application. One such formula used to treat a variety of diseases, including cancer, contains two herbs, whose main active components are Halofuginone (HF) and Artemisinin (ATS). Here we studied the anticancer synergism of HF and ATS in various cancer cell lines and in a xenograft nude mice model. We found that the HF-ATS combination arrested more cells at the G1/G0 Phase than either one alone, with the concomitant increased levels of CDK2 inhibitors, p21 Cip1 and p27 Kip1 . By knocking down p21 Cip1 and p27 Kip1 separately or simultaneously in HCT116 cells and MCF-7 cells, we found that p21 Cip1 was required for HF induced G1/G0 arrest, whereas p21 Cip1 and p27 Kip1 were both required for ATS or HF-ATS combination-mediated cell cycle arrest. Moreover, HF-ATS combination synergistically inhibited tumor growth in xenograft nude mice, and this was associated with the increased levels of p21 Cip1 and p27 Kip1 . Collectively, these data indicate that the upregulation of p21 Cip1 and p27 Kip1 contributes to the synergistic anticancer effect of the HF-ATS combination.
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halofuginone and artemisinin synergistically arrest cancer cells at the g1 G0 Phase by upregulating p21 cip1 and p27 kip1
Oncotarget, 2016Co-Authors: Guoqing Chen, Ruihong Gong, Dajian Yang, Ge Zhang, Aiping Lu, Zhaoxiang BianAbstract:// Guoqing Chen 1, 2, * , Ruihong Gong 1, * , Xianli Shi 3 , Dajian Yang 2 , Ge Zhang 1 , Aiping Lu 1 , Jianbo Yue 3 , Zhaoxiang Bian 1 1 School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China 2 Chongqing Academy of Chinese Materia Medica, Chongqing, China 3 Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China * These authors have contributed equally to this work Correspondence to: Jianbo Yue, email: jianbyue@cityu.edu.hk Zhaoxiang Bian, email: bzxiang@hkbu.edu.hk Keywords: halofuginone, artemisinin, synergy, cell proliferation, cell cycle Received: February 24, 2016 Accepted: June 9, 2016 Published: July 1, 2016 ABSTRACT Combinational drug therapy is one of the most promising strategies in modern anticancer research. Traditional Chinese medicine (TCM) formulas represent a wealth of complex combinations proven successful over centuries of clinical application. One such formula used to treat a variety of diseases, including cancer, contains two herbs, whose main active components are Halofuginone (HF) and Artemisinin (ATS). Here we studied the anticancer synergism of HF and ATS in various cancer cell lines and in a xenograft nude mice model. We found that the HF-ATS combination arrested more cells at the G1/G0 Phase than either one alone, with the concomitant increased levels of CDK2 inhibitors, p21 Cip1 and p27 Kip1 . By knocking down p21 Cip1 and p27 Kip1 separately or simultaneously in HCT116 cells and MCF-7 cells, we found that p21 Cip1 was required for HF induced G1/G0 arrest, whereas p21 Cip1 and p27 Kip1 were both required for ATS or HF-ATS combination-mediated cell cycle arrest. Moreover, HF-ATS combination synergistically inhibited tumor growth in xenograft nude mice, and this was associated with the increased levels of p21 Cip1 and p27 Kip1 . Collectively, these data indicate that the upregulation of p21 Cip1 and p27 Kip1 contributes to the synergistic anticancer effect of the HF-ATS combination.
Kuniharu Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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bex2 suppresses mitochondrial activity and is required for dormant cancer stem cell maintenance in intrahepatic cholangiocarcinoma
Scientific Reports, 2020Co-Authors: Keiichi Tamai, Mao Nakamurashima, Rie Shibuyatakahashi, Shin Ichiro Kanno, Akira Yasui, Mai Mochizuki, Wataru Iwai, Yuta Wakui, Makoto Abue, Kuniharu YamamotoAbstract:Cancer stem cells (CSCs) define a subpopulation of cancer cells that are resistant to therapy. However, little is known of how CSC characteristics are regulated. We previously showed that dormant cancer stem cells are enriched with a CD274low fraction of cholangiocarcinoma cells. Here we found that BEX2 was highly expressed in CD274low cells, and that BEX2 knockdown decreased the tumorigenicity and G0 Phase of cholangiocarcinoma cells. BEX2 was found to be expressed predominantly in G0 Phase and starvation induced the USF2 transcriptional factor, which induced BEX2 transcription. Comprehensive screening of BEX2 binding proteins identified E3 ubiquitin ligase complex proteins, FEM1B and CUL2, and a mitochondrial protein TUFM, and further demonstrated that knockdown of BEX2 or TUFM increased mitochondria-related oxygen consumption and decreased tumorigenicity in cholangiocarcinoma cells. These results suggest that BEX2 is essential for maintaining dormant cancer stem cells through the suppression of mitochondrial activity in cholangiocarcinoma.
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bex2 suppresses mitochondrial activity and is required for dormant cancer stem cell maintenance in intrahepatic cholangiocarcinoma
Social Science Research Network, 2020Co-Authors: Keiichi Tamai, Mao Nakamurashima, Rie Shibuyatakahashi, Shin Ichiro Kanno, Akira Yasui, Mai Mochizuki, Wataru Iwai, Yuta Wakui, Makoto Abue, Kuniharu YamamotoAbstract:Cancer stem cells (CSCs) define a subpopulation of cancer cells that are resistant to therapy. However, little is known of how CSC characteristics are regulated. We previously showed that dormant cancer stem cells are enriched with a CD274low fraction of cholangiocarcinoma cells. Here we found that BEX2 was highly expressed in CD274low cells, and that BEX2 knockdown decreased the tumorigenicity and G0 Phase of cholangiocarcinoma cells. BEX2 was found to be expressed predominantly in G0 Phase and starvation induced the USF2 transcriptional factor, which induced BEX2 transcription. Comprehensive screening of BEX2 binding proteins identified E3 ubiquitin ligase complex proteins, FEM1B and CUL2, and a mitochondrial protein TUFM, and further demonstrated that knockdown of BEX2 or TUFM increased mitochondria-related oxygen consumption and decreased tumorigenicity in cholangiocarcinoma cells. These results suggest that BEX2 is essential for maintaining dormant cancer stem cells through the suppression of mitochondrial activity in cholangiocarcinoma. Funding Statement: This research was supported in part by the Biomedical Research Core of Tohoku University Graduate School of Medicine. This research was supported in part by JSPS KAKENHI grant numbers JP: 19K08430, 17K10716, and 16K07132, and Practical Research for Innovative Cancer Control from AMED by grant number JP17ck0106197, The Cooperative Research Project Program of Joint Usage/Research Center at The Institute of Development, Aging and Cancer, Tohoku University, and Takeda Medical Foundation. Declaration of Interests: There are no financial conflicts of interest. Ethics Approval Statement: This study was conducted according to the principles expressed in the Declaration of Helsinki and was approved by the Ethics Committees at Miyagi Cancer Center (Natori, Japan) and Tohoku University Graduate School of Medicine (Sendai, Japan). The protocol of animal experiments was approved by the Miyagi Cancer Center Animal Care and Use Committee (permit number: MCC-AE-2019-8).
Xingyi Zhang - One of the best experts on this subject based on the ideXlab platform.
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dracorhodin perchlorate induces g1 G0 Phase arrest and mitochondria mediated apoptosis in sk mes 1 human lung squamous carcinoma cells
Oncology Letters, 2015Co-Authors: Guangxin Zhang, Yifan Zhang, Ranji Cui, Mei Sun, Peiyan Hua, Xingyi ZhangAbstract:Dracorhodin perchlorate (DP) has recently been revealed to induce apoptosis in various types of cancer. However, the antitumor potential and molecular mechanisms of DP in human lung cancer have not been previously reported. Therefore, the present study aimed to investigate the effects of DP on cell viability, the cell cycle and apoptosis, using an MTT assay, flow cytometry and western blot studies. DP was identified to induce cellular and DNA morphological changes, and decreased the viability of SK-MES-1 human lung squamous carcinoma cells. DP significantly inhibited the growth of SK-MES-1 cells by inducing apoptosis and G1/G0 cell cycle arrest in a dose-dependent manner via activation of p53 (P<0.05). Furthermore, DP promoted the significant upregulation of B cell lymphoma-2 (Bcl-2)-activated X protein and significant downregulation of Bcl-2 (P<0.05), inducing dissipation of the mitochondrial membrane potential (MMP). In addition, caspase-3 was activated by DP via the cleavage of its substrate, proteolytic cleavage of poly(ADP-ribose) polymerase. DP also induced caspase-independent apoptosis by significantly increasing the protein expression of the apoptosis-inducing factor (P<0.05), which is localized in mitochondria under the physiological conditions and released into the cytoplasm when MMP is dissipated. Furthermore, the present study demonstrated that DP significantly increased the generation of reactive oxygen species (P<0.05). In conclusion, the current study revealed that DP is able to induce cell cycle arrest and apoptosis in SK-MES-1 cells via activation of the mitochondrial pathway, indicating that DP may be a potential leading compound for the development of future lung cancer therapeutic regimes.
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alantolactone induces apoptosis and cell cycle arrest on lung squamous cancer sk mes 1 cells
Journal of Biochemical and Molecular Toxicology, 2015Co-Authors: Peng Zhao, Zhenxiang Pan, Yungang Luo, Leilei Zhang, Guangxin Zhang, Yifan Zhang, Ranji Cui, Mei Sun, Xingyi ZhangAbstract:Alantolactone, a sesquiterpene lactone compound, has variety of pharmacological properties, including anti-inflammatory and antineoplastic effects. In our study, alantolactone inhibited cancer cell proliferation. To explore the mechanisms underlying its antitumor action, we further examined apoptotic cells and cell cycle distribution using flow cytometry analysis. Alantolactone triggered apoptosis and induced cell cycle G1/G0 Phase arrest. Furthermore, the expressions of caspases-8, -9, -3, PARP, and Bax were significantly upregulated, while antiapoptotic factor Bcl-2 expression was inhibited. In addition, the expressions of cyclin-dependent kinase 4 (CDK4), CDK6, cyclin D3, and cyclin D1 were downregulated by alantolactone. Therefore, our findings indicated that alantolactone has an antiproliferative role on lung squamous cancer cells, and it may be a promising chemotherapeutic agent for squamous lung cancer SK-MES-1 cells.
Aurelio Serrano - One of the best experts on this subject based on the ideXlab platform.
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inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through nad depletion in fermenting yeast
Journal of Biological Chemistry, 2013Co-Authors: Gloria Serranobueno, Agustin Hernandez, Guillermo Lopezlluch, Jose R Perezcastineira, Placido Navas, Aurelio SerranoAbstract:Abstract Inorganic pyrophosphatases are required for the anabolism to take place in all living organisms. Defects in genes encoding these hydrolytic enzymes are considered inviable, although its exact nature has not been studied at cellular and molecular physiology levels. Using a conditional mutant in IPP1, the Saccharomyces cerevisiae gene encoding the cytosolic soluble pyrophosphatase, we show that respiring cells arrest in S-Phase upon Ipp1p deficiency but they remain viable and resume growth if accumulated pyrophosphate is removed. However, fermenting cells arrest in G1/G0 Phase and suffer massive vacuolisation and eventual cell death by autophagy. Impaired NAD+ metabolism is a major determinant of cell death in this scenario since demise can be avoided under conditions favouring accumulation of the oxidised pyridine coenzyme. These results posit that the mechanisms related to excess pyrophosphate toxicity in eukaryotes are dependent on the cell's energy metabolism.
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inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through nad depletion in fermenting yeast
Journal of Biological Chemistry, 2013Co-Authors: Gloria Serranobueno, Agustin Hernandez, Guillermo Lopezlluch, Jose R Perezcastineira, Placido Navas, Aurelio SerranoAbstract:Inorganic pyrophosphatases are required for anabolism to take place in all living organisms. Defects in genes encoding these hydrolytic enzymes are considered inviable, although their exact nature has not been studied at the cellular and molecular physiology levels. Using a conditional mutant in IPP1, the Saccharomyces cerevisiae gene encoding the cytosolic soluble pyrophosphatase, we show that respiring cells arrest in S Phase upon Ipp1p deficiency, but they remain viable and resume growth if accumulated pyrophosphate is removed. However, fermenting cells arrest in G1/G0 Phase and suffer massive vacuolization and eventual cell death by autophagy. Impaired NAD+ metabolism is a major determinant of cell death in this scenario because demise can be avoided under conditions favoring accumulation of the oxidized pyridine coenzyme. These results posit that the mechanisms related to excess pyrophosphate toxicity in eukaryotes are dependent on the energy metabolism of the cell.
Agustin Hernandez - One of the best experts on this subject based on the ideXlab platform.
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inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through nad depletion in fermenting yeast
Journal of Biological Chemistry, 2013Co-Authors: Gloria Serranobueno, Agustin Hernandez, Guillermo Lopezlluch, Jose R Perezcastineira, Placido Navas, Aurelio SerranoAbstract:Abstract Inorganic pyrophosphatases are required for the anabolism to take place in all living organisms. Defects in genes encoding these hydrolytic enzymes are considered inviable, although its exact nature has not been studied at cellular and molecular physiology levels. Using a conditional mutant in IPP1, the Saccharomyces cerevisiae gene encoding the cytosolic soluble pyrophosphatase, we show that respiring cells arrest in S-Phase upon Ipp1p deficiency but they remain viable and resume growth if accumulated pyrophosphate is removed. However, fermenting cells arrest in G1/G0 Phase and suffer massive vacuolisation and eventual cell death by autophagy. Impaired NAD+ metabolism is a major determinant of cell death in this scenario since demise can be avoided under conditions favouring accumulation of the oxidised pyridine coenzyme. These results posit that the mechanisms related to excess pyrophosphate toxicity in eukaryotes are dependent on the cell's energy metabolism.
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inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through nad depletion in fermenting yeast
Journal of Biological Chemistry, 2013Co-Authors: Gloria Serranobueno, Agustin Hernandez, Guillermo Lopezlluch, Jose R Perezcastineira, Placido Navas, Aurelio SerranoAbstract:Inorganic pyrophosphatases are required for anabolism to take place in all living organisms. Defects in genes encoding these hydrolytic enzymes are considered inviable, although their exact nature has not been studied at the cellular and molecular physiology levels. Using a conditional mutant in IPP1, the Saccharomyces cerevisiae gene encoding the cytosolic soluble pyrophosphatase, we show that respiring cells arrest in S Phase upon Ipp1p deficiency, but they remain viable and resume growth if accumulated pyrophosphate is removed. However, fermenting cells arrest in G1/G0 Phase and suffer massive vacuolization and eventual cell death by autophagy. Impaired NAD+ metabolism is a major determinant of cell death in this scenario because demise can be avoided under conditions favoring accumulation of the oxidized pyridine coenzyme. These results posit that the mechanisms related to excess pyrophosphate toxicity in eukaryotes are dependent on the energy metabolism of the cell.