Document Type
Article
Publication Date
9-18-2015
Publication Title
Oncotarget
Abstract
Prostate cancer is the second most commonly diagnosed cancer among men in the United States. Prostate cancer therapy is severely hampered by lack of response and development of resistance to conventional chemotherapeutic drugs in patients. Therefore, the development and discovery of new drugs have become an urgent clinical need. Interferons (IFNs), a family of pleiotropic cytokines, exert antitumor activities due to their anti-proliferative, immunomodulatory and proapoptotic functions. Here, we report that pretreatment of prostate cancer PC-3 cells with IFNs sensitized these cells to double-stranded RNAs (dsRNAs)-induced apoptosis. The enhancement effect of IFN treatment was dependent on IFN subtypes, in particular, IFN γ. In comparison with IFN α or β, IFN γ treatment remarkably augmented apoptosis in PC-3 cells induced with polyinosinic:polycytidylic acid (poly I:C), a synthesized form of dsRNA. We demonstrated that IFN-signaling was necessary for these effects by using mutant cell lines. Transfection of 2–5A, the activator of RNase L, or silencing of dsRNA-dependent protein kinase R (PKR) by siRNA did not have any significant impact on this event, suggesting that neither RNase L nor PKR was involved in poly I:C/IFN γ-induced apoptosis in the cells. Further investigation of the apoptotic pathway revealed that Bak, a pro-apoptotic member of the Bcl-2family, was synergistically up-regulated by IFN γ and poly I:C, whereas other members of the family were not affected. Knocking down of Bak demonstrated its contribution to poly I:C/IFN γ-induced apoptosis in the cells. We believeour findings will precipitate the design of novel therapeutic strategies for prostate cancer.
Recommended Citation
Tan, Haiyan; Zeng, Chun; Xie, Junbo; Alghamdi, Norah J.; Song, Ya; Zhang, Hongbing; Zhou, Aimin; and Jin, Di, "Effects of Interferons and Double-Stranded RNA on Human Prostate Cancer Cell Apoptosis" (2015). Chemistry Faculty Publications. 387.
https://engagedscholarship.csuohio.edu/scichem_facpub/387
DOI
10.18632/oncotarget.5508
Version
Publisher's PDF
Volume
6
Issue
36
Comments
This work was supported by the Faculty Development Fund, and Dr. John C. Vitullo's Pilot and Bridge Funding Program, Cleveland State University, to AZ and National Natural Science Foundation of China 81301900 to DJ.