Research Papers:

This article has been corrected. Correction in: Oncotarget. 2019; 10:6044-6044.

Effects of interferons and double-stranded RNA on human prostate cancer cell apoptosis

Haiyan Tan, Chun Zeng, Junbo Xie, Norah J. Alghamdi, Ya Song, Hongbing Zhang, Aimin Zhou and Di Jin _

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Oncotarget. 2015; 6:39184-39195. https://doi.org/10.18632/oncotarget.5508

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Haiyan Tan2, Chun Zeng2, Junbo Xie4, Norah J. Alghamdi2, Ya Song5, Hongbing Zhang1, Aimin Zhou2,3, Di Jin1

1Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China

2Clinical Chemistry Program, Department of Chemistry, Cleveland State University, Cleveland, OH, USA

3Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, OH, USA

4College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, China

5College of basic medical sciences, Dalian Medical University, Dalian, China

Correspondence to:

Di Jin, e-mail: [email protected]

Aimin Zhou, e-mail: [email protected]

Keywords: interferon, double-stranded RNA, apoptosis, prostate cancer, signaling

Received: January 31, 2015     Accepted: September 18, 2015     Published: October 01, 2015


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.

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