title: Effects of interferons and double-stranded RNA on human prostate cancer cell apoptosis.
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.
authors.affiliation: Clinical Chemistry Program, Department of Chemistry, Cleveland State University, Cleveland, OH, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Tan
authors.affiliation: Clinical Chemistry Program, Department of Chemistry, Cleveland State University, Cleveland, OH, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Zeng
authors.affiliation: College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Xie
authors.affiliation: Clinical Chemistry Program, Department of Chemistry, Cleveland State University, Cleveland, OH, USA.
authors.forename: Norah J
authors.initials: NJ
authors.lastname: Alghamdi
authors.affiliation: College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Song
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Clinical Chemistry Program, Department of Chemistry, Cleveland State University, Cleveland, OH, USA.|Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, OH, USA.
authors.forename: Aimin
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors.forename: Di
authors.initials: D
authors.lastname: Jin
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D011070:Poly I-C / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D012330:RNA, Double-Stranded; D015398:Signal Transduction
chemical_list: D012330:RNA, Double-Stranded; D007371:Interferon-gamma; D011070:Poly I-C
keywords: apoptosis; double-stranded RNA; interferon; prostate cancer; signaling