Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives

Resistance to chemotherapy in cancer patients has been correlated to the overexpression of the ATPbinding 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 stemofol...

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Main Authors: Sonthaya Umsumarng, Komsak Pintha, Pornsiri Pitchakarn, Kwankamol Sastraruji, Thanapat Sastraruji, Alison T. Ung, Araya Jatisatienr, Stephen G. Pyne, Pornngarm Limtrakul
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Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/52399
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Institution: Chiang Mai University
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spelling th-cmuir.6653943832-523992018-09-04T09:35:50Z Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives Sonthaya Umsumarng Komsak Pintha Pornsiri Pitchakarn Kwankamol Sastraruji Thanapat Sastraruji Alison T. Ung Araya Jatisatienr Stephen G. Pyne Pornngarm Limtrakul Chemistry Pharmacology, Toxicology and Pharmaceutics Resistance to chemotherapy in cancer patients has been correlated to the overexpression of the ATPbinding 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. © 2013 The Pharmaceutical Society of Japan. 2018-09-04T09:24:46Z 2018-09-04T09:24:46Z 2013-04-01 Journal 13475223 00092363 2-s2.0-84876493908 10.1248/cpb.c12-00967 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84876493908&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/52399
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Chemistry
Pharmacology, Toxicology and Pharmaceutics
spellingShingle Chemistry
Pharmacology, Toxicology and Pharmaceutics
Sonthaya Umsumarng
Komsak Pintha
Pornsiri Pitchakarn
Kwankamol Sastraruji
Thanapat Sastraruji
Alison T. Ung
Araya Jatisatienr
Stephen G. Pyne
Pornngarm Limtrakul
Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives
description Resistance to chemotherapy in cancer patients has been correlated to the overexpression of the ATPbinding 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. © 2013 The Pharmaceutical Society of Japan.
format Journal
author Sonthaya Umsumarng
Komsak Pintha
Pornsiri Pitchakarn
Kwankamol Sastraruji
Thanapat Sastraruji
Alison T. Ung
Araya Jatisatienr
Stephen G. Pyne
Pornngarm Limtrakul
author_facet Sonthaya Umsumarng
Komsak Pintha
Pornsiri Pitchakarn
Kwankamol Sastraruji
Thanapat Sastraruji
Alison T. Ung
Araya Jatisatienr
Stephen G. Pyne
Pornngarm Limtrakul
author_sort Sonthaya Umsumarng
title Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives
title_short Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives
title_full Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives
title_fullStr Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives
title_full_unstemmed Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives
title_sort inhibition of p-glycoprotein mediated multidrug resistance by stemofoline derivatives
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84876493908&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/52399
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