title: Inhibition of Transient Receptor Potential Melastain 7 Enhances Apoptosis Induced by TRAIL in PC-3 cells.
abstract: Transient receptor potential melastain 7 (TRPM7) is a bifunctional protein with dual structure of both ion channel and protein kinase, participating in a wide variety of diseases including cancer. Recent researches have reported the mechanism of TRPM7 in human cancers. However, the correlation between TRPM7 and prostate cancer (PCa) has not been well studied. The objective of this study was to investigate the potential the role of TRPM7 in the apoptosis of PC-3 cells, which is the key cell of advanced metastatic PCa. In this study, we demonstrated the influence and potential function of TRPM7 on the PC-3 cells apoptosis induced by TNF-related apoptosis inducing-ligand (TRAIL). The study also found a novel up-regulated expression of TRPM7 in PC-3 cells after treating with TRAIL. Suppression of TRPM7 by TRPM7 non-specific inhibitors (Gd3+ or 2-aminoethoxy diphenylborate (2-APB) ) not only markedly eliminated TRPM7 expression level, but also increased the apoptosis of TRAIL-treated PC-3 cells, which may be regulated by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway accompany with up-regulated expression of cleaved Caspase-3, (TRAIL-receptor 1, death receptors 4) DR4, and (TRAIL-receptor 2, death receptors 5) DR5. Taken together, our findings strongly suggested that TRPM7 was involved in the apoptosis of PC-3 cells induced by TRAIL, indicating that TRPM7 may be applied as a therapeutic target for PCa.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China E-mail : liang_chaozhao@163.com.
authors.forename: Chang-Ming
authors.initials: CM
authors.lastname: Lin
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Ma
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Zong-Yao
authors.initials: ZY
authors.lastname: Hao
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Zhou
authors.forename: Hao-Qiang
authors.initials: HQ
authors.lastname: Shi
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Zhang
authors.forename: En-Ming
authors.initials: EM
authors.lastname: Shao
authors.forename: Chao-Zhao
authors.initials: CZ
authors.lastname: Liang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001896:Boron Compounds / Q000494:pharmacology; D045744:Cell Line, Tumor; D005682:Gadolinium / Q000494:pharmacology; D006801:Humans; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001896:Boron Compounds; D005682:Gadolinium; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand; D050053:TRPM Cation Channels; C109986:2-aminoethoxydiphenyl borate; C486583:TRPM7 protein, human