Jining Medical University, Jining, Shandong Province, People's Republic of China.
Mol Cell Biochem. 2012 Feb;361(1-2):47-54. doi: 10.1007/s11010-011-1086-9. Epub 2011 Sep 29.
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.
大多数转移性黑色素瘤对不同的化疗药物具有抗药性，因此，迫切需要寻找新型的抗黑色素瘤药物和辅助药物。在这里，我们发现 1-苯基-2-癸酰氨基-3-吗啉-1-丙醇（PDMP），一种糖脂生物合成抑制剂，可增强两种黑色素瘤细胞系（WM-115 和 B16）中姜黄素诱导的细胞生长抑制和凋亡。PDMP 促进了姜黄素诱导的神经酰胺积累，后者有助于黑色素瘤细胞凋亡。PDMP 还显著增强了姜黄素诱导的 c-Jun N-末端激酶的激活，这对黑色素瘤细胞凋亡很重要。同时，姜黄素联合 PDMP 治疗可显著抑制促生存 PI3K/AKT 信号通路的激活。总之，PDMP 增强了姜黄素诱导的黑色素瘤细胞生长抑制和凋亡，这归因于多种信号事件的变化。联合使用 PDMP 和姜黄素可能代表了一种针对黑色素瘤的新的治疗干预措施。
