Combination of HDAC inhibitor TSA and silibinin induces cell cycle arrest and apoptosis by targeting survivin and cyclinB1/Cdk1 in pancreatic cancer cells

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Wan FengXiaoping Zou

Abstract

Histone deacetylases (HDAC) are involved in diverse biological processes and therefore emerge as potential targets for pancreatic cancer. Silibinin, an active component of silymarin, is known to inhibit growth of pancreatic cancer in vivo and in vitro. Herein, we examined the cytotoxic effects of TSA in combination with silibinin and investigated the possible mechanism in two pancreatic cancer cell lines (Panc1 and Capan2). Our study found that combination treatment of HDAC inhibitor and silibinin exerted additive growth inhibitory effect on pancreatic cancer cell. Annexin V-FITC/PI staining and flow cytometry analysis demonstrated that combination therapy induced G2/M cell cycle arrest and apoptosis in Panc1and Capan2 cells. The induction of apoptosis was further confirmed by evaluating the activation of caspases. Moreover, treatment with TSA and silibinin resulted in a profound reduction in the expression of cyclinA2, cyclinB1/Cdk1 and survivin. Taken together, our study might indicate that the novel combination of HDAC inhibitor and silibinin could offer therapeutic potential against pancreatic cancer.

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Citations

Dec 25, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zhan ShiXiaoqing Sun
Jan 11, 2018·Science China. Life Sciences·Hui LyuBolin Liu
Nov 23, 2018·Science China. Life Sciences·Yesheng YinXiaobo Qiu
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Nov 8, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jingjing WuEnhua Wang
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Apr 3, 2021·Molecular Biology Reports·Shruti GuptaKiran Kumar Tejavath
Aug 17, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Maryam FallahHamed Mirzaei

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