Yin Yang-1 increases apoptosis through Bax activation in pancreatic cancer cells
نویسندگان
چکیده
The transcriptional regulator Yin Yang-1 (YY1) is a tumor suppressor known to be overexpressed in pancreatic cancer. We found that overexpression of YY1 promoted apoptosis and increased the expression and mitochondrial localization of the pro-apoptotic Bax protein in pancreatic cancer cell lines. Luciferase reporter, electrophoretic mobility shift (EMSA), and chromatin immunoprecipitation (ChIP) assays revealed binding of YY1 to the BAX promoter. Moreover, YY1 promoted pancreatic cancer cell apoptosis through Bax transcriptional activation and subsequent translocation of Bax to the mitochondrial membrane, leading to cytochrome c release, and caspase activation.YY1 and BAX are co-expressed in pancreatic cancer tissues and higher BAX expression predicts better outcomes for patients. The ability of YY1 to promote apoptosis in pancreatic cancer cells suggests it may represent a valuable diagnostic and therapeutic target.
منابع مشابه
An Effective Concentration of 5-Aza-CdR to Induce Cell Death and Apoptosis in Human Pancreatic Cancer Cell Line through Reactivating RASSF1A and Up-Regulation of Bax Genes
Background: Promoter hyper-methylation of tumor suppressor genes is a common event that occurs in cancer. As methylation is a reversible modification, agents capable of reversing an abnormal methylation status should help to combat cancer. 5-Aza-CdR is a DNA methyl-transferase inhibitor. The present study aimed to evaluate the effect of 5-Aza-CdR on the proliferation of human pancreatic cancer ...
متن کاملMatrine inhibits diethylnitrosamine-induced HCC proliferation in rats through inducing apoptosis via p53, Bax-dependent caspase-3 activation pathway and down-regulating MLCK overexpression
The proliferation of hepatocellular carcinoma (HCC) cells is one of the leading causes of liver cancer mortality in humans. The inhibiting effects of matrine on HCC cell proliferation have been studied, but the mechanism of that inhibition has not been fully elucidated. Since, apoptosis plays an important role in HCC cell proliferation. We examined the apoptosis-inducing effect of matrine on tu...
متن کاملMatrine inhibits diethylnitrosamine-induced HCC proliferation in rats through inducing apoptosis via p53, Bax-dependent caspase-3 activation pathway and down-regulating MLCK overexpression
The proliferation of hepatocellular carcinoma (HCC) cells is one of the leading causes of liver cancer mortality in humans. The inhibiting effects of matrine on HCC cell proliferation have been studied, but the mechanism of that inhibition has not been fully elucidated. Since, apoptosis plays an important role in HCC cell proliferation. We examined the apoptosis-inducing effect of matrine on tu...
متن کاملSynergistic Effect of Fluorouracil Combined With Harmin on Induction of Apoptosis in Aspc-1 Cell Line And The Expression of Apoptotic Genes (Bax, P53 And Caspase3 &9)
Introduction: Pancreatic cancer is one of the deadliest cancers of the digestive system in the world. Due to the increasing resistance of cancer cells to chemotherapy and its side effects, there is a need for drugs with fewer side effects and natural origin. Methods: In this study, the effect of harmine and its concomitant use with fluorouracil to induce apoptosis in pancreatic cancer cells, A...
متن کاملWild Type p53 Gene Transfer Increases Chemosensitivity and Apoptotic Response of PANC-1 Pancreatic Tumor Cell Line
The effect of p53 gene therapy on chemosensitivity and apoptotic response of PANC-1 tumor cells, which express high amount of mutant p53, to cancer chemotherapeutic agents of Etoposide and Doxorubicin was investigated. Comparison of the chemosensitivity of PANC-1 cells to its wild type p53 transfectants showed that wt-p53 expressing transfectants are more sensitive to both Etoposide and Doxorub...
متن کامل