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Fazlul H Sarkar - One of the best experts on this subject based on the ideXlab platform.
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tw 37 a small molecule inhibitor of bcl 2 inhibits Cell Growth and induces apoptosis in pancreatic cancer involvement of notch 1 signaling pathway
Cancer Research, 2009Co-Authors: Zhiwei Wang, Asfar S Azmi, Aamir Ahmad, Sanjeev Banerjee, Shaomeng Wang, Fazlul H Sarkar, Ramzi M MohammadAbstract:Overexpression of Bcl-2 family proteins has been found in a variety of aggressive human carcinomas, including pancreatic cancer, suggesting that specific agents targeting Bcl-2 family proteins would be valuable for pancreatic cancer therapy. We have previously reported that TW-37, a small-molecule inhibitor of Bcl-2 family proteins, inhibited Cell Growth and induced apoptosis in pancreatic cancer. However, the precise role and the molecular mechanism of action of TW-37 have not been fully elucidated. In our current study, we found that TW-37 induces Cell Growth Inhibition and S-phase Cell cycle arrest, with regulation of several important Cell cycle-related genes like p27, p57, E2F-1, cdc25A, CDK4, cyclin A, cyclin D1, and cyclin E. The Cell Growth Inhibition was accompanied by increased apoptosis with concomitant attenuation of Notch-1, Jagged-1, and its downstream genes such as Hes-1 in vitro and in vivo. We also found that down-regulation of Notch-1 by small interfering RNA or gamma-secretase inhibitors before TW-37 treatment resulted in enhanced Cell Growth Inhibition and apoptosis. Our data suggest that the observed antitumor activity of TW-37 is mediated through a novel pathway involving inactivation of Notch-1 and Jagged-1.
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notch 1 down regulation by curcumin is associated with the Inhibition of Cell Growth and the induction of apoptosis in pancreatic cancer Cells
Cancer, 2006Co-Authors: M Zhiwei D Wang, Sanjeev Banerjee, Yuxiang Zhang, M Yiwei D Li, Fazlul H SarkarAbstract:BACKGROUND Notch signaling plays a critical role in maintaining the balance between Cell proliferation, differentiation, and apoptosis, and thereby may contribute to the development of pancreatic cancer. Therefore, the down-regulation of Notch signaling may be a novel approach for pancreatic cancer therapy. It has been reported that curcumin down-regulates many genes that are known to promote survival and also up-regulates genes that are known promoters of apoptosis in pancreatic cancer Cells in vitro. It also has been reported that there is cross-talk between Notch-1 and another major Cell Growth and apoptotic regulatory pathway, the nuclear factor κB (NF-κB) pathway, which is down-regulated by both curcumin and reduction of Notch-1 levels. However, to the authors' knowledge to date, no studies have determined whether the down-regulation of Notch-1 signaling, resulting in the inactivation of NF-κB activity, contributes to curcumin-induced Cell Growth Inhibition and apoptosis in pancreatic cancer Cells. METHODS The authors used multiple molecular approaches, such as the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, an apoptosis assay, gene transfection, real-time reverse transcriptase-polymerase chain reaction analysis, Western blot analysis, and an electrophoretic mobility shift assay to measure the DNA binding activity of NF-κB. RESULTS Curcumin inhibited Cell Growth and induced apoptosis in pancreatic cancer Cells. Notch-1, Hes-1, and Bcl-XL expression levels concomitantly were down-regulated by curcumin treatment. These results correlated with the inactivation of NF-κB activity and increased apoptosis induced by curcumin. The down-regulation of Notch-1 by small-interfering RNA prior to curcumin treatment resulted in enhanced Cell Growth Inhibition and apoptosis. CONCLUSIONS The current results provide the first demonstration to the authors' knowledge that the Notch-1 signaling pathway is associated mechanistically with NF-κB activity during curcumin-induced Cell Growth Inhibition and apoptosis of pancreatic Cells. These results suggest that the down-regulation of Notch signaling by curcumin may be a novel strategy for the treatment of patients with pancreatic cancer. Cancer 2006. © 2006 American Cancer Society.
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down regulation of notch 1 contributes to Cell Growth Inhibition and apoptosis in pancreatic cancer Cells
Molecular Cancer Therapeutics, 2006Co-Authors: Zhiwei Wang, Sanjeev Banerjee, Yuxiang Zhang, Joshua Liao, Fazlul H SarkarAbstract:Pancreatic cancer remains the fourth most common cause of cancer-related death in the United States. Notch signaling plays a critical role in maintaining the balance among Cell proliferation, differentiation, and apoptosis, and thereby may contribute to the development of pancreatic cancer. To characterize Notch pathway function in pancreatic cancer Cells, we explored the consequences of down-regulation of Notch-1 in BxPC-3, HPAC, and PANC-1 pancreatic cancer Cells. Using multiple Cellular and molecular approaches such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis assay, flow cytometry, gene transfection, real-time reverse transcription-PCR (RT-PCR), Western blotting, and electrophoretic mobility shift assay for measuring DNA binding activity of nuclear factor κB (NF-κB), we found that down-regulation of Notch-1 inhibited Cell Growth and induced apoptosis in pancreatic cancer Cells. Notch-1 down-regulation also increased Cell population in the G-G1 phase. Compared with control, small interfering RNA–transfected Cells decreased expression of cyclin A, cyclin D1, and cyclin-dependent kinase 2. We found up-regulation of p21 and p27, which was correlated with the Cell cycle changes. In addition, Notch-1 down-regulation also induced apoptosis, which could be due to decreased Bcl-2 and Bcl-XL protein expression in pancreatic cancer Cells. Because Notch-1 is known to cross-talk with another major Cell Growth and apoptotic regulatory pathway (i.e., NF-κB), we found that NF-κB is a downstream target of Notch because down-regulation of Notch reduced NF-κB activity. We also found that genistein, a prominent isoflavone, could be an active agent for the down-regulation of the Notch pathway. These findings suggest that Notch-1 down-regulation, especially by genistein, could be a novel therapeutic approach for the treatment of pancreatic cancer. [Mol Cancer Ther 2006;5(3):483–93]
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down regulation of notch 1 contributes to Cell Growth Inhibition and apoptosis in pancreatic cancer Cells
Molecular Cancer Therapeutics, 2006Co-Authors: Zhiwei Wang, Sanjeev Banerjee, Yuxiang Zhang, Joshua Liao, Fazlul H SarkarAbstract:Pancreatic cancer remains the fourth most common cause of cancer-related death in the United States. Notch signaling plays a critical role in maintaining the balance among Cell proliferation, differentiation, and apoptosis, and thereby may contribute to the development of pancreatic cancer. To characterize Notch pathway function in pancreatic cancer Cells, we explored the consequences of down-regulation of Notch-1 in BxPC-3, HPAC, and PANC-1 pancreatic cancer Cells. Using multiple Cellular and molecular approaches such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis assay, flow cytometry, gene transfection, real-time reverse transcription-PCR (RT-PCR), Western blotting, and electrophoretic mobility shift assay for measuring DNA binding activity of nuclear factor kappaB (NF-kappaB), we found that down-regulation of Notch-1 inhibited Cell Growth and induced apoptosis in pancreatic cancer Cells. Notch-1 down-regulation also increased Cell population in the G(0)-G(1) phase. Compared with control, small interfering RNA-transfected Cells decreased expression of cyclin A, cyclin D1, and cyclin-dependent kinase 2. We found up-regulation of p21 and p27, which was correlated with the Cell cycle changes. In addition, Notch-1 down-regulation also induced apoptosis, which could be due to decreased Bcl-2 and Bcl-X(L) protein expression in pancreatic cancer Cells. Because Notch-1 is known to cross-talk with another major Cell Growth and apoptotic regulatory pathway (i.e., NF-kappaB), we found that NF-kappaB is a downstream target of Notch because down-regulation of Notch reduced NF-kappaB activity. We also found that genistein, a prominent isoflavone, could be an active agent for the down-regulation of the Notch pathway. These findings suggest that Notch-1 down-regulation, especially by genistein, could be a novel therapeutic approach for the treatment of pancreatic cancer.
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indole 3 carbinol i3c induced Cell Growth Inhibition g1 Cell cycle arrest and apoptosis in prostate cancer Cells
Oncogene, 2001Co-Authors: Sreenivasa R Chinni, Sunil Upadhyay, Prathima Koppolu, Fazlul H SarkarAbstract:Prostate cancer is one of the most common cancers in men and it is the second leading cause of cancer related death in men in the United States. Recent dietary and epidemiological studies have suggested the benefit of dietary intake of fruits and vegetables in lowering the incidence of prostate cancer. A diet rich in fruits and vegetables provides phytochemicals, particularly indole-3-carbinol (I3C), which may be responsible for the prevention of many types of cancer, including hormone-related cancers such as prostate. Studies to elucidate the role and the molecular mechanism(s) of action of I3C in prostate cancer, however, have not been conducted. In the current study, we investigated whether I3C had any effect against prostate cancer Cells and, if so, attempts were made to identify the potential molecular mechanism(s) by which I3C elicits its biological effects on prostate cancer Cells. Here we report for the first time that I3C inhibits the Growth of PC-3 prostate cancer Cells. Induction of G1 Cell cycle arrest was also observed in PC-3 Cells treated with I3C, which may be due to the observed effects of I3C in the up-regulation of p21(WAF1) and p27(Kip1) CDK inhibitors, followed by their association with cyclin D1 and E and down-regulation of CDK6 protein kinase levels and activity. The induction of p21(WAF1) appears to be transcriptionally upregulated and independent of the p53 responsive element. In addition, I3C inhibited the hyperpohosphorylation of the Retinoblastoma (Rb) protein in PC-3 Cells. Induction of apoptosis was also observed in this Cell line when treated with I3C, as measured by DNA laddering and poly (ADP-ribose) polymersae (PARP) cleavage. We also found an up-regulation of Bax, and down-regulation of Bcl-2 in I3C-treated Cells. These effects may also be mediated by the down-regulation of NF-kappaB observed in I3C treated PC-3 Cells. From these results, we conclude that I3C inhibits the Growth of PC-3 prostate cancer Cells by inducing G1 Cell cycle arrest leading to apoptosis, and regulates the expression of apoptosis-related genes. These findings suggest that I3C may be an effective chemopreventive or therapeutic agent against prostate cancer.
Fraidoon Kavoosi - One of the best experts on this subject based on the ideXlab platform.
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effect of zebularine in comparison to and in combination with trichostatin a on cip kip family p21cip1 waf1 sdi1 p27kip1 and p57kip2 dnmts dnmt1 dnmt3a and dnmt3b class i hdacs hdacs 1 2 3 and class ii hdacs hdacs 4 5 6 gene expression Cell Growth in
Asian Pacific Journal of Cancer Prevention, 2020Co-Authors: Masumeh Sanaei, Fraidoon KavoosiAbstract:Background A pattern of epigenetic modifications and changes, DNA methylation and histone modification, is central to many human cancers. A variety of tumor suppressor genes (TSGs) have been demonstrated to be silenced because of histone deacetylation and DNA hypermethylation in several cancers. Recent in vitro studies have shown that two known mechanisms of epigenetic alteration consisting of methylation and histone deacetylation seem to be the best candidate mechanisms for inactivation of CIP/KIP family (p21Cip1/Waf1/Sdi1, and p27Kip1) in numerous cancers. Numerous investigations have indicated that DNA demethylating and histone deacetylase inhibitors (HDACIs) can restore the CIP/KIP family gene expression. Previously, we evaluated the effect of trichostatin A (TSA) and 5-aza-2'-deoxycytidine (5-AZA-CdR) on hepatoCellular carcinoma (HCC). The present study was designed to investigate the effect of zebularine in comparison to and in combination with trichostatin A on p21Cip1/Waf1/Sdi1, p27Kip1, p57Kip2, DNMT1, DNMT3a and DNMT3b, Class I HDACs (HDACs 1, 2, 3) and Class II HDACs (HDACs 4, 5, 6) gene expression, Cell Growth Inhibition and apoptosis induction in colon cancer LS 174T Cell line. Materials and methods The colon cancer LS 174T Cell line was cultured and treated with zebularine and TSA. To determine Cell viability, apoptosis, and the relative expression level of the genes, MTT assay, Cell apoptosis assay, and qRT-PCR were done respectively. Results Both compounds significantly inhibited Cell Growth, and induced apoptosis. Furthermore, both compounds increased p21Cip1/Waf1/Sdi1, p27Kip1, and p57Kip2 significantly. Additionally, zebularine and TSA decreased DNMTs and HDACs gene expression respectively. Conclusion The zebularine and trichostatin A can reactivate the CIP/KIP family through Inhibition of DNMTs and HDACs genes activity.
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the effect of 5 aza 2 deoxycytidine in combination to and in comparison with vorinostat on dna methyltransferases histone deacetylase 1 glutathione s transferase 1 and suppressor of cytokine signaling 1 genes expression Cell Growth Inhibition and apo
International journal of hematology-oncology and stem cell research, 2020Co-Authors: Masumeh Sanaei, Fraidoon Kavoosi, Zahra EsmiAbstract:Background: Aberrant methylation and histone deacetylation of tumor suppressor genes (TSGs) are the most epigenetic alterations involving in tumorigenesis. Overexpression of DNA methyltransferases (DNMTs) and histone deacetylase 1 (HDAC1) have been reported in several cancers. The reversion of hypermethylation and deacetylation by epi-drugs such as 5-aza-2'-deoxycytidine (5-AZA-CdR) and vorinostat (SAHA) can restore normal expression of TSGs. Previously, we reported that 5-AZA-CdR and valproic acid (VPA) can inhibit DNMT1 in hepatoCellular carcinoma (HCC). The aim of this study was to investigate the effect of 5-AZA-CdR in combination to and in comparison with SAHA on DNMT1, DNMT3a, DNMT3b, histone deacetylase 1 (HDAC1), glutathione S-transferase 1 (GSTP1) and suppressor of cytokine signaling 1 (SOCS1) genes expression, Cell Growth Inhibition and apoptotic induction in hepatoCellular LCL-PI 11 Cell line. Materials and Methods: The Cells were treated with 5-AZA-CdR and SAHA and then MTT assay, Cell apoptosis assay and Real-time quantitative RT-PCR (qRT-PCR) were done. Results: Both agents indicated significant inhibitory and apoptotic effect (P< 0.001). The apoptotic effect of SAHA was more than that of 5-Aza-CdR. The result of qRT-PCR indicated that 5-Aza-CdR decreased DNMT1, DNMT3a, DNMT3b and increased GSTP1and SOCS1 genes expression and SAHA decreased HDAC1 and increased GSTP1 and SOCS1 genes expression significantly. Maximal apoptosis and genes expression were seen with combined treatment. Conclusion: 5-AZA-CdR and SAHA down-regulated DNMT1, DNMT3a, DNMT3b, and HDAC1 and up-regulated GSTP1 and SOCS1 gene expression by which inhibited Cell viability and induced apoptosis, suggesting that they could be used in the treatment of HCC.
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effect of 5 aza 2 deoxycytidine in comparison to valproic acid and trichostatin a on histone deacetylase 1 dna methyltransferase 1 and cip kip family p21 p27 and p57 genes expression Cell Growth Inhibition and apoptosis induction in colon cancer sw48
Advanced Biomedical Research, 2019Co-Authors: Masumeh Sanaei, Fraidoon KavoosiAbstract:Background: Cancer initiation and progression depends on genetic and epigenetic alterations such as DNA methylation and histone modifications. Hypermethylation and deacetylation of the CIP/KIP family (p21, p27, and p57) lead to tumorigenesis. Our previous study indicated that DNA methyltransferase (DNMT) inhibitor and histone deacetylase (HDAC) inhibitors can inhibit Cell Growth and induce apoptosis. The aim of the present study was to investigate the effect of 5-Aza-2'-deoxycytidine (5-Aza-CdR) in comparison to valproic acid (VPA) and trichostatin A (TSA) on HDAC1, DNMT1, and CIP/KIP family (p21, p27, and p57) genes expression, Cell Growth Inhibition, and apoptosis induction in colon cancer SW480 Cell line. Materials and Methods: The effect of the compounds on the Cell viability was measured by MTT assay. The expression of HDAC1, DNMT1, and CIP/KIP family (p21, p27, and p57) genes was evaluated by real-time quantitative reverse transcription- polymerase chain reaction (RT-PCR). For the detection of Cell apoptosis, apoptotic Cells were examined by the Annexin V-FITC/PI detection kit. Results: The results of MTT assay indicated that 5-Aza-CdR, VPA, and TSA significantly inhibited Cell Growth (P
Zhiwei Wang - One of the best experts on this subject based on the ideXlab platform.
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tw 37 a small molecule inhibitor of bcl 2 inhibits Cell Growth and induces apoptosis in pancreatic cancer involvement of notch 1 signaling pathway
Cancer Research, 2009Co-Authors: Zhiwei Wang, Asfar S Azmi, Aamir Ahmad, Sanjeev Banerjee, Shaomeng Wang, Fazlul H Sarkar, Ramzi M MohammadAbstract:Overexpression of Bcl-2 family proteins has been found in a variety of aggressive human carcinomas, including pancreatic cancer, suggesting that specific agents targeting Bcl-2 family proteins would be valuable for pancreatic cancer therapy. We have previously reported that TW-37, a small-molecule inhibitor of Bcl-2 family proteins, inhibited Cell Growth and induced apoptosis in pancreatic cancer. However, the precise role and the molecular mechanism of action of TW-37 have not been fully elucidated. In our current study, we found that TW-37 induces Cell Growth Inhibition and S-phase Cell cycle arrest, with regulation of several important Cell cycle-related genes like p27, p57, E2F-1, cdc25A, CDK4, cyclin A, cyclin D1, and cyclin E. The Cell Growth Inhibition was accompanied by increased apoptosis with concomitant attenuation of Notch-1, Jagged-1, and its downstream genes such as Hes-1 in vitro and in vivo. We also found that down-regulation of Notch-1 by small interfering RNA or gamma-secretase inhibitors before TW-37 treatment resulted in enhanced Cell Growth Inhibition and apoptosis. Our data suggest that the observed antitumor activity of TW-37 is mediated through a novel pathway involving inactivation of Notch-1 and Jagged-1.
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down regulation of notch 1 contributes to Cell Growth Inhibition and apoptosis in pancreatic cancer Cells
Molecular Cancer Therapeutics, 2006Co-Authors: Zhiwei Wang, Sanjeev Banerjee, Yuxiang Zhang, Joshua Liao, Fazlul H SarkarAbstract:Pancreatic cancer remains the fourth most common cause of cancer-related death in the United States. Notch signaling plays a critical role in maintaining the balance among Cell proliferation, differentiation, and apoptosis, and thereby may contribute to the development of pancreatic cancer. To characterize Notch pathway function in pancreatic cancer Cells, we explored the consequences of down-regulation of Notch-1 in BxPC-3, HPAC, and PANC-1 pancreatic cancer Cells. Using multiple Cellular and molecular approaches such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis assay, flow cytometry, gene transfection, real-time reverse transcription-PCR (RT-PCR), Western blotting, and electrophoretic mobility shift assay for measuring DNA binding activity of nuclear factor κB (NF-κB), we found that down-regulation of Notch-1 inhibited Cell Growth and induced apoptosis in pancreatic cancer Cells. Notch-1 down-regulation also increased Cell population in the G-G1 phase. Compared with control, small interfering RNA–transfected Cells decreased expression of cyclin A, cyclin D1, and cyclin-dependent kinase 2. We found up-regulation of p21 and p27, which was correlated with the Cell cycle changes. In addition, Notch-1 down-regulation also induced apoptosis, which could be due to decreased Bcl-2 and Bcl-XL protein expression in pancreatic cancer Cells. Because Notch-1 is known to cross-talk with another major Cell Growth and apoptotic regulatory pathway (i.e., NF-κB), we found that NF-κB is a downstream target of Notch because down-regulation of Notch reduced NF-κB activity. We also found that genistein, a prominent isoflavone, could be an active agent for the down-regulation of the Notch pathway. These findings suggest that Notch-1 down-regulation, especially by genistein, could be a novel therapeutic approach for the treatment of pancreatic cancer. [Mol Cancer Ther 2006;5(3):483–93]
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down regulation of notch 1 contributes to Cell Growth Inhibition and apoptosis in pancreatic cancer Cells
Molecular Cancer Therapeutics, 2006Co-Authors: Zhiwei Wang, Sanjeev Banerjee, Yuxiang Zhang, Joshua Liao, Fazlul H SarkarAbstract:Pancreatic cancer remains the fourth most common cause of cancer-related death in the United States. Notch signaling plays a critical role in maintaining the balance among Cell proliferation, differentiation, and apoptosis, and thereby may contribute to the development of pancreatic cancer. To characterize Notch pathway function in pancreatic cancer Cells, we explored the consequences of down-regulation of Notch-1 in BxPC-3, HPAC, and PANC-1 pancreatic cancer Cells. Using multiple Cellular and molecular approaches such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis assay, flow cytometry, gene transfection, real-time reverse transcription-PCR (RT-PCR), Western blotting, and electrophoretic mobility shift assay for measuring DNA binding activity of nuclear factor kappaB (NF-kappaB), we found that down-regulation of Notch-1 inhibited Cell Growth and induced apoptosis in pancreatic cancer Cells. Notch-1 down-regulation also increased Cell population in the G(0)-G(1) phase. Compared with control, small interfering RNA-transfected Cells decreased expression of cyclin A, cyclin D1, and cyclin-dependent kinase 2. We found up-regulation of p21 and p27, which was correlated with the Cell cycle changes. In addition, Notch-1 down-regulation also induced apoptosis, which could be due to decreased Bcl-2 and Bcl-X(L) protein expression in pancreatic cancer Cells. Because Notch-1 is known to cross-talk with another major Cell Growth and apoptotic regulatory pathway (i.e., NF-kappaB), we found that NF-kappaB is a downstream target of Notch because down-regulation of Notch reduced NF-kappaB activity. We also found that genistein, a prominent isoflavone, could be an active agent for the down-regulation of the Notch pathway. These findings suggest that Notch-1 down-regulation, especially by genistein, could be a novel therapeutic approach for the treatment of pancreatic cancer.
Masumeh Sanaei - One of the best experts on this subject based on the ideXlab platform.
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effect of zebularine in comparison to and in combination with trichostatin a on cip kip family p21cip1 waf1 sdi1 p27kip1 and p57kip2 dnmts dnmt1 dnmt3a and dnmt3b class i hdacs hdacs 1 2 3 and class ii hdacs hdacs 4 5 6 gene expression Cell Growth in
Asian Pacific Journal of Cancer Prevention, 2020Co-Authors: Masumeh Sanaei, Fraidoon KavoosiAbstract:Background A pattern of epigenetic modifications and changes, DNA methylation and histone modification, is central to many human cancers. A variety of tumor suppressor genes (TSGs) have been demonstrated to be silenced because of histone deacetylation and DNA hypermethylation in several cancers. Recent in vitro studies have shown that two known mechanisms of epigenetic alteration consisting of methylation and histone deacetylation seem to be the best candidate mechanisms for inactivation of CIP/KIP family (p21Cip1/Waf1/Sdi1, and p27Kip1) in numerous cancers. Numerous investigations have indicated that DNA demethylating and histone deacetylase inhibitors (HDACIs) can restore the CIP/KIP family gene expression. Previously, we evaluated the effect of trichostatin A (TSA) and 5-aza-2'-deoxycytidine (5-AZA-CdR) on hepatoCellular carcinoma (HCC). The present study was designed to investigate the effect of zebularine in comparison to and in combination with trichostatin A on p21Cip1/Waf1/Sdi1, p27Kip1, p57Kip2, DNMT1, DNMT3a and DNMT3b, Class I HDACs (HDACs 1, 2, 3) and Class II HDACs (HDACs 4, 5, 6) gene expression, Cell Growth Inhibition and apoptosis induction in colon cancer LS 174T Cell line. Materials and methods The colon cancer LS 174T Cell line was cultured and treated with zebularine and TSA. To determine Cell viability, apoptosis, and the relative expression level of the genes, MTT assay, Cell apoptosis assay, and qRT-PCR were done respectively. Results Both compounds significantly inhibited Cell Growth, and induced apoptosis. Furthermore, both compounds increased p21Cip1/Waf1/Sdi1, p27Kip1, and p57Kip2 significantly. Additionally, zebularine and TSA decreased DNMTs and HDACs gene expression respectively. Conclusion The zebularine and trichostatin A can reactivate the CIP/KIP family through Inhibition of DNMTs and HDACs genes activity.
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the effect of 5 aza 2 deoxycytidine in combination to and in comparison with vorinostat on dna methyltransferases histone deacetylase 1 glutathione s transferase 1 and suppressor of cytokine signaling 1 genes expression Cell Growth Inhibition and apo
International journal of hematology-oncology and stem cell research, 2020Co-Authors: Masumeh Sanaei, Fraidoon Kavoosi, Zahra EsmiAbstract:Background: Aberrant methylation and histone deacetylation of tumor suppressor genes (TSGs) are the most epigenetic alterations involving in tumorigenesis. Overexpression of DNA methyltransferases (DNMTs) and histone deacetylase 1 (HDAC1) have been reported in several cancers. The reversion of hypermethylation and deacetylation by epi-drugs such as 5-aza-2'-deoxycytidine (5-AZA-CdR) and vorinostat (SAHA) can restore normal expression of TSGs. Previously, we reported that 5-AZA-CdR and valproic acid (VPA) can inhibit DNMT1 in hepatoCellular carcinoma (HCC). The aim of this study was to investigate the effect of 5-AZA-CdR in combination to and in comparison with SAHA on DNMT1, DNMT3a, DNMT3b, histone deacetylase 1 (HDAC1), glutathione S-transferase 1 (GSTP1) and suppressor of cytokine signaling 1 (SOCS1) genes expression, Cell Growth Inhibition and apoptotic induction in hepatoCellular LCL-PI 11 Cell line. Materials and Methods: The Cells were treated with 5-AZA-CdR and SAHA and then MTT assay, Cell apoptosis assay and Real-time quantitative RT-PCR (qRT-PCR) were done. Results: Both agents indicated significant inhibitory and apoptotic effect (P< 0.001). The apoptotic effect of SAHA was more than that of 5-Aza-CdR. The result of qRT-PCR indicated that 5-Aza-CdR decreased DNMT1, DNMT3a, DNMT3b and increased GSTP1and SOCS1 genes expression and SAHA decreased HDAC1 and increased GSTP1 and SOCS1 genes expression significantly. Maximal apoptosis and genes expression were seen with combined treatment. Conclusion: 5-AZA-CdR and SAHA down-regulated DNMT1, DNMT3a, DNMT3b, and HDAC1 and up-regulated GSTP1 and SOCS1 gene expression by which inhibited Cell viability and induced apoptosis, suggesting that they could be used in the treatment of HCC.
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effect of 5 aza 2 deoxycytidine in comparison to valproic acid and trichostatin a on histone deacetylase 1 dna methyltransferase 1 and cip kip family p21 p27 and p57 genes expression Cell Growth Inhibition and apoptosis induction in colon cancer sw48
Advanced Biomedical Research, 2019Co-Authors: Masumeh Sanaei, Fraidoon KavoosiAbstract:Background: Cancer initiation and progression depends on genetic and epigenetic alterations such as DNA methylation and histone modifications. Hypermethylation and deacetylation of the CIP/KIP family (p21, p27, and p57) lead to tumorigenesis. Our previous study indicated that DNA methyltransferase (DNMT) inhibitor and histone deacetylase (HDAC) inhibitors can inhibit Cell Growth and induce apoptosis. The aim of the present study was to investigate the effect of 5-Aza-2'-deoxycytidine (5-Aza-CdR) in comparison to valproic acid (VPA) and trichostatin A (TSA) on HDAC1, DNMT1, and CIP/KIP family (p21, p27, and p57) genes expression, Cell Growth Inhibition, and apoptosis induction in colon cancer SW480 Cell line. Materials and Methods: The effect of the compounds on the Cell viability was measured by MTT assay. The expression of HDAC1, DNMT1, and CIP/KIP family (p21, p27, and p57) genes was evaluated by real-time quantitative reverse transcription- polymerase chain reaction (RT-PCR). For the detection of Cell apoptosis, apoptotic Cells were examined by the Annexin V-FITC/PI detection kit. Results: The results of MTT assay indicated that 5-Aza-CdR, VPA, and TSA significantly inhibited Cell Growth (P
Sanjeev Banerjee - One of the best experts on this subject based on the ideXlab platform.
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tw 37 a small molecule inhibitor of bcl 2 inhibits Cell Growth and induces apoptosis in pancreatic cancer involvement of notch 1 signaling pathway
Cancer Research, 2009Co-Authors: Zhiwei Wang, Asfar S Azmi, Aamir Ahmad, Sanjeev Banerjee, Shaomeng Wang, Fazlul H Sarkar, Ramzi M MohammadAbstract:Overexpression of Bcl-2 family proteins has been found in a variety of aggressive human carcinomas, including pancreatic cancer, suggesting that specific agents targeting Bcl-2 family proteins would be valuable for pancreatic cancer therapy. We have previously reported that TW-37, a small-molecule inhibitor of Bcl-2 family proteins, inhibited Cell Growth and induced apoptosis in pancreatic cancer. However, the precise role and the molecular mechanism of action of TW-37 have not been fully elucidated. In our current study, we found that TW-37 induces Cell Growth Inhibition and S-phase Cell cycle arrest, with regulation of several important Cell cycle-related genes like p27, p57, E2F-1, cdc25A, CDK4, cyclin A, cyclin D1, and cyclin E. The Cell Growth Inhibition was accompanied by increased apoptosis with concomitant attenuation of Notch-1, Jagged-1, and its downstream genes such as Hes-1 in vitro and in vivo. We also found that down-regulation of Notch-1 by small interfering RNA or gamma-secretase inhibitors before TW-37 treatment resulted in enhanced Cell Growth Inhibition and apoptosis. Our data suggest that the observed antitumor activity of TW-37 is mediated through a novel pathway involving inactivation of Notch-1 and Jagged-1.
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notch 1 down regulation by curcumin is associated with the Inhibition of Cell Growth and the induction of apoptosis in pancreatic cancer Cells
Cancer, 2006Co-Authors: M Zhiwei D Wang, Sanjeev Banerjee, Yuxiang Zhang, M Yiwei D Li, Fazlul H SarkarAbstract:BACKGROUND Notch signaling plays a critical role in maintaining the balance between Cell proliferation, differentiation, and apoptosis, and thereby may contribute to the development of pancreatic cancer. Therefore, the down-regulation of Notch signaling may be a novel approach for pancreatic cancer therapy. It has been reported that curcumin down-regulates many genes that are known to promote survival and also up-regulates genes that are known promoters of apoptosis in pancreatic cancer Cells in vitro. It also has been reported that there is cross-talk between Notch-1 and another major Cell Growth and apoptotic regulatory pathway, the nuclear factor κB (NF-κB) pathway, which is down-regulated by both curcumin and reduction of Notch-1 levels. However, to the authors' knowledge to date, no studies have determined whether the down-regulation of Notch-1 signaling, resulting in the inactivation of NF-κB activity, contributes to curcumin-induced Cell Growth Inhibition and apoptosis in pancreatic cancer Cells. METHODS The authors used multiple molecular approaches, such as the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, an apoptosis assay, gene transfection, real-time reverse transcriptase-polymerase chain reaction analysis, Western blot analysis, and an electrophoretic mobility shift assay to measure the DNA binding activity of NF-κB. RESULTS Curcumin inhibited Cell Growth and induced apoptosis in pancreatic cancer Cells. Notch-1, Hes-1, and Bcl-XL expression levels concomitantly were down-regulated by curcumin treatment. These results correlated with the inactivation of NF-κB activity and increased apoptosis induced by curcumin. The down-regulation of Notch-1 by small-interfering RNA prior to curcumin treatment resulted in enhanced Cell Growth Inhibition and apoptosis. CONCLUSIONS The current results provide the first demonstration to the authors' knowledge that the Notch-1 signaling pathway is associated mechanistically with NF-κB activity during curcumin-induced Cell Growth Inhibition and apoptosis of pancreatic Cells. These results suggest that the down-regulation of Notch signaling by curcumin may be a novel strategy for the treatment of patients with pancreatic cancer. Cancer 2006. © 2006 American Cancer Society.
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down regulation of notch 1 contributes to Cell Growth Inhibition and apoptosis in pancreatic cancer Cells
Molecular Cancer Therapeutics, 2006Co-Authors: Zhiwei Wang, Sanjeev Banerjee, Yuxiang Zhang, Joshua Liao, Fazlul H SarkarAbstract:Pancreatic cancer remains the fourth most common cause of cancer-related death in the United States. Notch signaling plays a critical role in maintaining the balance among Cell proliferation, differentiation, and apoptosis, and thereby may contribute to the development of pancreatic cancer. To characterize Notch pathway function in pancreatic cancer Cells, we explored the consequences of down-regulation of Notch-1 in BxPC-3, HPAC, and PANC-1 pancreatic cancer Cells. Using multiple Cellular and molecular approaches such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis assay, flow cytometry, gene transfection, real-time reverse transcription-PCR (RT-PCR), Western blotting, and electrophoretic mobility shift assay for measuring DNA binding activity of nuclear factor κB (NF-κB), we found that down-regulation of Notch-1 inhibited Cell Growth and induced apoptosis in pancreatic cancer Cells. Notch-1 down-regulation also increased Cell population in the G-G1 phase. Compared with control, small interfering RNA–transfected Cells decreased expression of cyclin A, cyclin D1, and cyclin-dependent kinase 2. We found up-regulation of p21 and p27, which was correlated with the Cell cycle changes. In addition, Notch-1 down-regulation also induced apoptosis, which could be due to decreased Bcl-2 and Bcl-XL protein expression in pancreatic cancer Cells. Because Notch-1 is known to cross-talk with another major Cell Growth and apoptotic regulatory pathway (i.e., NF-κB), we found that NF-κB is a downstream target of Notch because down-regulation of Notch reduced NF-κB activity. We also found that genistein, a prominent isoflavone, could be an active agent for the down-regulation of the Notch pathway. These findings suggest that Notch-1 down-regulation, especially by genistein, could be a novel therapeutic approach for the treatment of pancreatic cancer. [Mol Cancer Ther 2006;5(3):483–93]
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down regulation of notch 1 contributes to Cell Growth Inhibition and apoptosis in pancreatic cancer Cells
Molecular Cancer Therapeutics, 2006Co-Authors: Zhiwei Wang, Sanjeev Banerjee, Yuxiang Zhang, Joshua Liao, Fazlul H SarkarAbstract:Pancreatic cancer remains the fourth most common cause of cancer-related death in the United States. Notch signaling plays a critical role in maintaining the balance among Cell proliferation, differentiation, and apoptosis, and thereby may contribute to the development of pancreatic cancer. To characterize Notch pathway function in pancreatic cancer Cells, we explored the consequences of down-regulation of Notch-1 in BxPC-3, HPAC, and PANC-1 pancreatic cancer Cells. Using multiple Cellular and molecular approaches such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis assay, flow cytometry, gene transfection, real-time reverse transcription-PCR (RT-PCR), Western blotting, and electrophoretic mobility shift assay for measuring DNA binding activity of nuclear factor kappaB (NF-kappaB), we found that down-regulation of Notch-1 inhibited Cell Growth and induced apoptosis in pancreatic cancer Cells. Notch-1 down-regulation also increased Cell population in the G(0)-G(1) phase. Compared with control, small interfering RNA-transfected Cells decreased expression of cyclin A, cyclin D1, and cyclin-dependent kinase 2. We found up-regulation of p21 and p27, which was correlated with the Cell cycle changes. In addition, Notch-1 down-regulation also induced apoptosis, which could be due to decreased Bcl-2 and Bcl-X(L) protein expression in pancreatic cancer Cells. Because Notch-1 is known to cross-talk with another major Cell Growth and apoptotic regulatory pathway (i.e., NF-kappaB), we found that NF-kappaB is a downstream target of Notch because down-regulation of Notch reduced NF-kappaB activity. We also found that genistein, a prominent isoflavone, could be an active agent for the down-regulation of the Notch pathway. These findings suggest that Notch-1 down-regulation, especially by genistein, could be a novel therapeutic approach for the treatment of pancreatic cancer.