Modulation of multidrug resistance by three bisbenzyl-isoquinolines in comparison with verapamil.
OBJECTIVE
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.


CONCLUSIONS
MDR was modulated by Cyc, Insr, and Insn, due to the increase of intracellular Dox accumulation.
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D004317:Doxorubicin / Q000378:metabolism; D018432:Drug Resistance, Multiple; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D006801:Humans; D007546:Isoquinolines / Q000302:isolation & purification / Q000494:pharmacology*; D007624:KB Cells / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*