title: JWA enhances As₂O₃-induced tubulin polymerization and apoptosis via p38 in HeLa and MCF-7 cells.
abstract: Arsenic trioxide (As₂O₃) has potential anti-cancer activity against a wide range of carcinomas via apoptosis induction or oncoprotein degradation. The mechanisms involved are not fully elucidated. Here, we demonstrated that As₂O₃ induced-apoptosis in HeLa and MCF-7 cancer cells was in part triggered by tubulin polymerization. High expression of JWA promoted tubulin polymerization and increased the sensitivity of the cancer cells to As₂O₃. The activation of the p38 MAPK (mitogen-activated protein kinases) signaling pathway was found to contribute to JWA-promoted tubulin polymerization. Our results suggest that JWA may serve as an effective enhancer of microtubule-targeted As₂O₃ anti-cancer therapy.
authors.affiliation: Department of Molecular Cell Biology & Toxicology, The Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, People's Republic of China.
authors.forename: Lianlian
authors.initials: L
authors.lastname: Shen
authors.forename: Wenxia
authors.initials: W
authors.lastname: Xu
authors.forename: Aiping
authors.initials: A
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Ye
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D020868:Gene Silencing; D006131:Growth Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008856:Microscopy, Fluorescence; D010087:Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D010957:Plasmids; D058105:Polymerization / Q000187:drug effects*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000378:metabolism; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C484566:ARL6IP5 protein, human; D001152:Arsenicals; D006131:Growth Inhibitors; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D010087:Oxides; D034741:RNA, Small Interfering; D014404:Tubulin; D050257:Tubulin Modulators; D048051:p38 Mitogen-Activated Protein Kinases; D000077237:Arsenic Trioxide