CJY, an isoflavone, reverses P-glycoprotein-mediated multidrug-resistance in doxorubicin-resistant human myelogenous leukaemia (K562/DOX) cells.
In an effort to develop safe and effective multidrug-resistance (MDR) reversing agents, the effect of CJY, an isoflavone, on the P-glycoprotein (P-gp) function and P-gp-mediated MDR was evaluated in doxorubicin-resistant human myelogenous leukaemia (K562/DOX) cells. The results showed that CJY caused a marked increase in accumulation and a notable decrease in efflux of rhodamine 123 (Rh123). The inhibitory effect of the agent on P-gp function persisted for at least 120 min after removal of 2.5 microM CJY from the incubation medium. The doxorubicin-induced cytotoxicity, apoptosis and cell cycle perturbations were significantly potentiated by CJY. The intracellular accumulation of doxorubicin was also enhanced. The compound exhibited potent effects in-vitro on the reversal of P-gp-mediated MDR, suggesting that it could become a candidate as an effective MDR reversing agent in cancer chemotherapy.
Ji
Bian-Sheng
BS
Institute of Pharmacy, Henan University, Kaifeng 475001, China.
He
Ling
L
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005434:Flow Cytometry; D005453:Fluorescence; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D020014:K562 Cells; D020112:Rhodamine 123 / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; C523261:CJY compound; D007529:Isoflavones; D020112:Rhodamine 123; D004317:Doxorubicin