Knockdown of sensitive to apoptosis gene by small interfering RNA enhances the sensitivity of PC3 cells toward actinomycin D and etoposide.
Actinomycin D and etoposide induce the production of reactive oxygen species, which play an important causative role in apoptotic cell death. Sensitive to apoptosis gene (SAG) protein, a redox inducible zinc RING finger protein that protects mammalian cells from apoptosis by redox reagents, is a metal chelator and a potential reactive oxygen species scavenger. The present report show that knockdown of SAG expression in PC3 cells greatly enhances apoptosis induced by actinomycin D and etoposide. Transfection of human prostate cancer PC3 cells with SAG small interfering RNA (siRNA) markedly decreased the expression of SAG, enhancing the susceptibility of actinomycin D- and etoposide-induced apoptosis reflected by DNA fragmentation, cellular redox status and the modulation of apoptotic marker proteins. These results indicate that SAG may play an important role in regulating the apoptosis induced by actinomycin D and etoposide and the sensitizing effect of SAG siRNA on the apoptotic cell death of PC3 cells offers the possibility of developing a modifier of cancer chemotherapy.
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Korea.
Eun Sun
ES
Yang
Yun Jeong
YJ
Huh
Jeen-Woo
JW
Park
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D003609:Dactinomycin / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000037:antagonists & inhibitors / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D010084:Oxidation-Reduction / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics
D016166:Free Radical Scavengers; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D003609:Dactinomycin; D005047:Etoposide; C118307:RNF7 protein, human; D044767:Ubiquitin-Protein Ligases