Reversal of human multi-drug resistance leukaemic cells by stemofoline derivatives via inhibition of p-glycoprotein function

• Main Authors: Umsumarng,S., Pitchakarn,P., Sastraruji,K., Yodkeeree,S., Ung,A., Pyne,S.G., Limtrakul,P.N.
• Format: Article
• Published: Wiley-Blackwell 2015
• Subjects: Toxicology; Pharmacology
• Online Access: http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84926282977&origin=inward; http://cmuir.cmu.ac.th/handle/6653943832/38445
• Institution: Chiang Mai University

© 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Our previous study reported multi-drug resistance (MDR) reversing properties of synthetic stemofoline derivatives (STFD), OH-A1, NH-B6 and NH-D6 on P-glycoprotein (P-gp) overexpressing leukaemic cells (K562/Adr); however, the mechanism was unclear. In this study, we further investigated whether the STFD reverse MDR through either the inhibition of P-gp function or expression in K562/Adr cells, or both. The P-gp functional studies showed that the STFD increased the accumulation of calcein-AM, rhodamine 123 and [¹⁴C]-doxorubicin in K562/Adr cells, while the effects have not been seen in their parental sensitive cancer cell line (K562). Further, the STFD did not alter the P-gp expression as determined by Western blotting. This study concludes that the STFD reverse MDR via the inhibition of P-gp function. The efficacy of the STFD to inhibit P-gp function followed the order: NH-B6 > OH-A1 > NH-D6. These compounds could be introduced as candidate molecules for treating cancers exhibiting P-gp-mediated MDR.