Reversal of Human Multi‐Drug Resistance Leukaemic Cells by Stemofoline Derivatives via Inhibition of P‐Glycoprotein Function |
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| Authors: | Sonthaya Umsumarng Pornsiri Pitchakarn Kwankamol Sastraruji Supachai Yodkeeree Alison T. Ung Stephen G. Pyne Pornngarm Limtrakul |
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| Affiliation: | 1. Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand;2. School of Chemistry, University of Wollongong, Wollongong, NSW, Australia;3. School of Chemistry and Forensic Science, University of Technology Sydney, Sydney, NSW, Australia |
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| Abstract: | 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. |
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