Combination of HDAC inhibitor TSA and silibinin induces cell cycle arrest and apoptosis by targeting survivin and cyclinB1/Cdk1 in pancreatic cancer cells.
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.
Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, Jiangsu Province, China.
Wan
W
Feng
Medical school, Nanjing University, Nanjing, Jiangsu, China.
Dawei
D
Cai
Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, Jiangsu Province, China.
Bin
B
Zhang
Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, Jiangsu Province, China.
Guochun
G
Lou
Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, Jiangsu Province, China. Electronic address: zouxiaoping795@hotmail.com.
Xiaoping
X
Zou
D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D056744:Cyclin B1 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D000077022:Survivin
C107489:BIRC5 protein, human; D056744:Cyclin B1; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D051034:Inhibitor of Apoptosis Proteins; D012838:Silymarin; D000077022:Survivin; C012589:trichostatin A; D000077385:Silybin; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D020169:Caspases; D006655:Histone Deacetylases
Combination therapy; Histone deacetylase; Pancreatic cancer; Silibinin