Melanosomal sequestration of cytotoxic drugs contributes to the intractability of malignant melanomas
作者： K. G. Chen , J. C. Valencia , B. Lai , G. Zhang , J. K. Paterson
关键词:
摘要: Multidrug resistance mechanisms underlying the intractability of malignant melanomas remain largely unknown. In this study, we demonstrate that development multidrug in involves subcellular sequestration intracellular cytotoxic drugs such as cis-diaminedichloroplatinum II (cisplatin; CDDP). CDDP is initially sequestered organelles melanosomes, which significantly reduces its nuclear localization when compared with nonmelanoma/KB-3-1 epidermoid carcinoma cells. The melanosomal accumulation remarkably modulates melanogenesis through a pronounced increase tyrosinase activity. altered manifested an ≈8-fold both pigmentation and extracellular transport melanosomes containing CDDP. Thus, our experiments provide evidence contribute to refractory properties melanoma cells by sequestering increasing melanosome-mediated drug export. Preventing inhibiting functions may have great potential approach improving chemosensitivity
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