title: Zinc sensitizes prostate cancer cells to sorafenib and regulates the expression of Livin.
abstract: In prostate carcinogenesis, normal zinc-accumulating epithelial cells are transformed into malignant cells that do not accumulate zinc. Increased levels of zinc have been shown to induce apoptosis through a caspase-dependent mechanism with down-regulated anti-apoptotic proteins in prostate cancer cells. Our previous study showed that, as a member of the inhibitor of apoptosis proteins (IAPs) family, Livin could play an important role in the initiation of human prostate cancer and promote cell proliferation by altering the G1-S cell cycle transition. In the present study, we measured the apoptosis sensitivity of prostate cancer cells to zinc and sorafenib and found that zinc sensitized prostate cancer cells to sorafenib-induced apoptosis. Surprisingly, we also found that, unlike its counterparts Survivin and cIAP2, Livin was not decreased all the time; instead, it was compensatively increased in zinc-mediated apoptosis at 48 h in prostate cancer cells. Our results offer potential treatment combinations that may augment the effect of sorafenib, and also reveal, for the first time, that increased Livin expression may play a role in the early cell death response of prostate cancer cells to zinc.
authors: Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
authors: Xiaochi
authors: X
authors: Chen
authors: Xiangyu
authors: X
authors: Che
authors: Jianbo
authors: J
authors: Wang
authors: Feng
authors: F
authors: Chen
authors: Xuejian
authors: X
authors: Wang
authors: Zhiwei
authors: Z
authors: Zhang
authors: Bo
authors: B
authors: Fan
authors: Deyong
authors: D
authors: Yang
authors: Xishuang
authors: X
authors: Song
mesh_terms: D000199:Actins / Q000187:drug effects; D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis*; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000077157:Sorafenib; D019287:Zinc Sulfate / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D010671:Phenylurea Compounds; D009536:Niacinamide; D019287:Zinc Sulfate; D000077157:Sorafenib