Heparan sulfate proteoglycan-mediated entry pathway for charged tri-platinum compounds: differential cellular accumulation mechanisms for platinum.

ABSTRACT: We examined the mechanism of accumulation of charged polynuclear platinum complexes (PPCs) based on analogy of polyarginine interactions with the cell surface heparan sulfate proteoglycan (HSPG) family of protein-linked glycosoaminoglycan polysaccharides (GAGs). GAGS such as heparan sulfate (HS) and chondroitin sulfate (CS) mediate the cellular entry of many charged molecules. Fluorescence microscopy and flow cytometry showed that PPCs, but not the neutral cisplatin or oxaliplatin, blocked the cellular entry of TAMRA-R(9) (a nonarginine peptide, R(9)) coupled to the TAMRA fluorescent label 5-(and 6-)carboxytetramethylrhodamine) in Chinese hamster ovary (CHO), human colon carcinoma (HCT116), and osteosarcoma (SAOS-2) cells. Furthermore, detection of platinum accumulation in wt CHO, mutant C

SUBMITTER: Silva H 

PROVIDER: S-EPMC3367083 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature