MODULATION OF MULTIDRUG-RESISTANCE BY 3 BISBENZYL-ISOQUINOLINES IN COMPARISON WITH VERAPAMIL

AIM: To compare cycleanine (Cyc), insularine (Insr>, insulanoline (Ins n> and verapamil (Ver) in modulation of multidrug resistance (MDR) in vitro. METHODS: The cytotoxic effect was determined by 3-[4, 5-dimethy lthiazol-2-yl], 5-diphenyl tetarzolium bromide (MIT) assay. The intrac ellular doxorubincin (Dox) accumulation was assayed by spectrofluorome ter. RESULTS: Cyc, Insr, Insn, and Ver showed significant activities i n modulating Dox and vincristine resistances in acquired resistant MCF -7/Adr and KBv200 cell lines in a dose-dependent manner. Cyc, Insr, In sn, and Ver increased intracellular Dox accumulation in MCF-7/Adr cell s. Cyc and Insr had greater activities than Ver in modulating MDR, whi le Insn had similar activity to that of Ver. CONCLUSION: MDR was modul ated by Cyc, Insr, and Insn, due to the increase of intracellular Dox accumulation.