title: RNA interference targeting sensitive-to-apoptosis gene potentiates doxorubicin- and staurosporine-induced apoptosis of PC3 cells.
abstract: Several anticancer agents exert their cancer cell killing effects by generating reactive oxygen species (ROS). Thus, a combination of ROS-producing agents and the inhibition of ROS elimination promotes the death of cancer cells. The sensitive to apoptosis gene (SAG) protein, a redox-inducible protein and potential ROS scavenger, protects mammalian cells from redox agent-induced apoptosis. In the present study, we found that silencing of SAG expression in human prostate cancer PC3 cells by transfection with SAG small-interfering RNA (siRNA) markedly enhanced susceptibility to doxorubicin- and to staurosporine-induced apoptotic cell death. Furthermore, pre-treatment with the thiol antioxidant N-acetylcysteine suppressed increases in ROS and apoptosis. This study suggests that knockdown of SAG augments the apoptosis of PC3 cells exposed to doxorubicin or staurosporine presumably by increasing intracellular ROS levels.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, South Korea.
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Yang
authors.forename: Yun Jeong
authors.initials: YJ
authors.lastname: Huh
authors.forename: Jeen-Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors*
chemical_list: D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D004317:Doxorubicin; C118307:RNF7 protein, human; D044767:Ubiquitin-Protein Ligases; D019311:Staurosporine; D000111:Acetylcysteine