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Modulation of multidrug resistance by three bisbenzyl-isoquinolines in comparison with verapamil
Aim:
To compare cycleanine (Cyc), insularine (Insr), insulanoline (Insn) and verapamil (Ver) in modulation of multidrug resistance (MDR) in vitro.
Methods:
The cytotoxic effect was determined by 3-[4, 5-dimethylthiazol-2-yl], 5-diphenyl tetarzolium bromide (MTT) assay. The intracellular doxorubincin (Dox) accumulation was assayed by spectrofluorometer.
Results:
Cyc, Insr, Insn, and Ver showed significant activities in modulating Dox and vincristine resistances in acquired resistant MCF-7/Adr and KBv200 cell lines in a dose-dependent manner. Cyc, Insr, Insn, and Ver increased intracellular Dox accumulation in MCF-7/Adr cells. Cyc and Insr had greater activities than Ver in modulating MDR, while Insn had similar activity to that of Ver.
Conclusion:
MDR was modulated by Cyc, Insr, and Insn, due to the increase of intracellular Dox accumulation.