title: Overcoming biochemical pharmacologic mechanisms of platinum resistance with a texaphyrin-platinum conjugate.
abstract: In our effort to investigate further texaphyrin conjugation as a means of increasing delivery and accumulation of known anticancer platinum agents in cancer cells, we have continued our studies on the mode of action of a texaphyrin-platinum conjugate, particularly in cisplatin-resistant tumor cells that are characterized by several mechanisms of resistance, including reduced drug accumulation. Our results provide support for the proposal that intracellular platinum and Pt-DNA adduct levels were significantly increased using our conjugate relative to corresponding Pt controls. Moreover, no differences were found in cellular accumulation and Pt-DNA adduct formation between Pt sensitive and Pt resistant ovarian cells. As a result, resistance to the conjugate was lower than cisplatin in resistant cells. Based on these results we conclude that texaphyrin conjugation provides a promising strategy for overcoming biochemical pharmacologic mechanisms of resistance.
authors.affiliation: Department of Chemistry and Biochemistry, Texas Institute for Diagnostics and Drug Development, The University of Texas, Austin, TX 78712-0165, USA.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Arambula
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Sessler
authors.forename: Zahid H
authors.initials: ZH
authors.lastname: Siddik
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000473:pathology; D011166:Porphyrins / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011166:Porphyrins; C442892:texaphyrin