Melanosomal sequestration of cytotoxic drugs contributes to the intractability of malignant melanomas.

ABSTRACT: Multidrug resistance mechanisms underlying the intractability of malignant melanomas remain largely unknown. In this study, we demonstrate that the development of multidrug resistance in melanomas involves subcellular sequestration of intracellular cytotoxic drugs such as cis-diaminedichloroplatinum II (cisplatin; CDDP). CDDP is initially sequestered in subcellular organelles such as melanosomes, which significantly reduces its nuclear localization when compared with nonmelanoma/KB-3-1 epidermoid carcinoma cells. The melanosomal accumulation of CDDP remarkably modulates melanogenesis through a pronounced increase in tyrosinase activity. The altered melanogenesis manifested an approximately 8-fold increase in both intracellular pigmentation and extracellular transport of melanosomes contain

SUBMITTER: Chen KG 

PROVIDER: S-EPMC1502551 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature