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

Journal Article


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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.

UOW Authors


  •   Umsumarng, Sonthaya (external author)
  •   Pitchakarn, Pornsiri (external author)
  •   Sastraruji, Kwankamol (external author)
  •   Yodkeeree, Supachai (external author)
  •   Ung, Alison T. (external author)
  •   Pyne, Stephen
  •   Limtrakul, Pornngarm (external author)

Publication Date


  • 2015

Citation


  • Umsumarng, S., Pitchakarn, P., Sastraruji, K., Yodkeeree, S., Ung, A. T., Pyne, S. G. & Limtrakul, P. (2015). Reversal of human multi-drug resistance leukaemic cells by stemofoline derivatives via inhibition of p-glycoprotein function. Basic and Clinical Pharmacology and Toxicology, 116 (5), 390-397.

Scopus Eid


  • 2-s2.0-84926282977

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3756&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2735

Has Global Citation Frequency


Number Of Pages


  • 7

Start Page


  • 390

End Page


  • 397

Volume


  • 116

Issue


  • 5

Place Of Publication


  • United Kingdom

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.

UOW Authors


  •   Umsumarng, Sonthaya (external author)
  •   Pitchakarn, Pornsiri (external author)
  •   Sastraruji, Kwankamol (external author)
  •   Yodkeeree, Supachai (external author)
  •   Ung, Alison T. (external author)
  •   Pyne, Stephen
  •   Limtrakul, Pornngarm (external author)

Publication Date


  • 2015

Citation


  • Umsumarng, S., Pitchakarn, P., Sastraruji, K., Yodkeeree, S., Ung, A. T., Pyne, S. G. & Limtrakul, P. (2015). Reversal of human multi-drug resistance leukaemic cells by stemofoline derivatives via inhibition of p-glycoprotein function. Basic and Clinical Pharmacology and Toxicology, 116 (5), 390-397.

Scopus Eid


  • 2-s2.0-84926282977

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3756&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2735

Has Global Citation Frequency


Number Of Pages


  • 7

Start Page


  • 390

End Page


  • 397

Volume


  • 116

Issue


  • 5

Place Of Publication


  • United Kingdom