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Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives

Journal Article


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Abstract


  • Resistance to chemotherapy in cancer patients has been correlated to the overexpression of the ATP-binding cassette (ABC) drug transporters including P-glycoprotein (P-gp) that actively efflux chemotherapeutic drugs from cancer cells. We examined the mutidrug resistance reversing property of stemofoline derivatives in drug-resistance human cervical carcinoma (KB-V1) and human leukemic (K562/Adr) cell lines that overexpress P-gp. Didehydrostemofoline and eleven of its derivatives were synthesized and the cytotoxicity and their effect on doxorubicin, vinblastine and paclitaxel sensitivity in drug resistant (KB-V1 and K562/Adr) and drug sensitive (KB-3-1 and K562) cell lines by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were determined. We found that three out of the twelve stemofoline derivatives including OH-A1, NH-B6 and NH-D6 showed commitment efficiency to increase sensitivity to doxorubicin, vinblastine and paclitaxel in KB-V1 cells and increase sensitivity to doxorubicin, and paclitaxel in K562/Adr cells whereas the effects have not been seen in their parental sensitive cancer cell lines (KB-3-1 and K562). These results indicate that stemofoline derivatives reversed P-gp-mediated multidrug resistance in vitro, and thus could be developed as effective chemosensitizers to treat multidrug-resistant cancers. The molecular mechanism of modulation of P-gp would be further determined.

UOW Authors


  •   Umsumarng, Sonthaya (external author)
  •   Pintha, Komsak (external author)
  •   Pitchakarn, Pornsiri (external author)
  •   Sastraruji, Kwankamol (external author)
  •   Sastraruji, Thanapat (external author)
  •   Ung, Alison T. (external author)
  •   Jatisatienr, Araya (external author)
  •   Pyne, Stephen
  •   Limtrakul, Pornngarm (external author)

Publication Date


  • 2013

Citation


  • Umsumarng, S., Pintha, K., Pitchakarn, P., Sastraruji, K., Sastraruji, T., Ung, A. T., Jatisatienr, A., Pyne, S. G. & Limtrakul, P. (2013). Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives. Chemical and Pharmaceutical Bulletin, 61 (4), 399-404.

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1525&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/513

Number Of Pages


  • 5

Start Page


  • 399

End Page


  • 404

Volume


  • 61

Issue


  • 4

Abstract


  • Resistance to chemotherapy in cancer patients has been correlated to the overexpression of the ATP-binding cassette (ABC) drug transporters including P-glycoprotein (P-gp) that actively efflux chemotherapeutic drugs from cancer cells. We examined the mutidrug resistance reversing property of stemofoline derivatives in drug-resistance human cervical carcinoma (KB-V1) and human leukemic (K562/Adr) cell lines that overexpress P-gp. Didehydrostemofoline and eleven of its derivatives were synthesized and the cytotoxicity and their effect on doxorubicin, vinblastine and paclitaxel sensitivity in drug resistant (KB-V1 and K562/Adr) and drug sensitive (KB-3-1 and K562) cell lines by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were determined. We found that three out of the twelve stemofoline derivatives including OH-A1, NH-B6 and NH-D6 showed commitment efficiency to increase sensitivity to doxorubicin, vinblastine and paclitaxel in KB-V1 cells and increase sensitivity to doxorubicin, and paclitaxel in K562/Adr cells whereas the effects have not been seen in their parental sensitive cancer cell lines (KB-3-1 and K562). These results indicate that stemofoline derivatives reversed P-gp-mediated multidrug resistance in vitro, and thus could be developed as effective chemosensitizers to treat multidrug-resistant cancers. The molecular mechanism of modulation of P-gp would be further determined.

UOW Authors


  •   Umsumarng, Sonthaya (external author)
  •   Pintha, Komsak (external author)
  •   Pitchakarn, Pornsiri (external author)
  •   Sastraruji, Kwankamol (external author)
  •   Sastraruji, Thanapat (external author)
  •   Ung, Alison T. (external author)
  •   Jatisatienr, Araya (external author)
  •   Pyne, Stephen
  •   Limtrakul, Pornngarm (external author)

Publication Date


  • 2013

Citation


  • Umsumarng, S., Pintha, K., Pitchakarn, P., Sastraruji, K., Sastraruji, T., Ung, A. T., Jatisatienr, A., Pyne, S. G. & Limtrakul, P. (2013). Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives. Chemical and Pharmaceutical Bulletin, 61 (4), 399-404.

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1525&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/513

Number Of Pages


  • 5

Start Page


  • 399

End Page


  • 404

Volume


  • 61

Issue


  • 4