title: 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) facilitates curcumin-induced melanoma cell apoptosis by enhancing ceramide accumulation, JNK activation, and inhibiting PI3K/AKT activation.
abstract: The majority of metastatic melanomas are resistant to different chemotherapeutic agents, consequently, the search for novel anti-melanoma agents and adjuvant is urgent. Here, we found that 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), an inhibitor of glycosphingolipid biosynthesis, enhanced curcumin-induced cell growth inhibition and apoptosis in two melanoma cell lines (WM-115 and B16). PDMP facilitated curcumin-induced ceramide accumulation; the latter contributed to melanoma cell apoptosis. PDMP also dramatically enhanced curcumin-induced c-Jun N-terminal kinase activation, which was important to melanoma cell apoptosis. Meanwhile, curcumin plus PDMP treatment largely inhibited the activation of pro-survival PI3K/AKT signal pathway. In conclusion, PDMP-sensitized curcumin-induced melanoma cell growth inhibition and apoptosis in vitro due to changes of multiple signal events. Combining PDMP with curcumin may represent a new therapeutic intervention against melanoma.
authors.affiliation: Jining Medical University, Jining, Shandong Province, People's Republic of China. tengyu33@yahoo.com
authors.forename: Teng
authors.initials: T
authors.lastname: Yu
authors.forename: Jinchao
authors.initials: J
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Qiu
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002518:Ceramides / Q000378:metabolism*; D003474:Curcumin / Q000494:pharmacology*; D004357:Drug Synergism; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008545:Melanoma; D009025:Morpholines / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002518:Ceramides; D009025:Morpholines; C033110:RV 538; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D003474:Curcumin