Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives

Umsumarng, S; Pintha, K; Pitchakarn, P; Sastraruji, K; Sastraruji, T; Ung, AT; Jatisatienr, A; Pyne, SG; Limtrakul, P

Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives

Umsumarng, S Pintha, K Pitchakarn, P Sastraruji, K Sastraruji, T Ung, AT

Jatisatienr, A Pyne, SG Limtrakul, P

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Publication Type:: Journal Article
Citation:: Chemical and Pharmaceutical Bulletin, 2013, 61 (4), pp. 399 - 404
Issue Date:: 2013-04-01

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Field	Value	Language
dc.contributor.author	Umsumarng, S	en_US
dc.contributor.author	Pintha, K	en_US
dc.contributor.author	Pitchakarn, P	en_US
dc.contributor.author	Sastraruji, K	en_US
dc.contributor.author	Sastraruji, T	en_US
dc.contributor.author	Ung, AT https://orcid.org/0000-0002-5665-0702	en_US
dc.contributor.author	Jatisatienr, A	en_US
dc.contributor.author	Pyne, SG	en_US
dc.contributor.author	Limtrakul, P	en_US
dc.date.issued	2013-04-01	en_US
dc.identifier.citation	Chemical and Pharmaceutical Bulletin, 2013, 61 (4), pp. 399 - 404	en_US
dc.identifier.issn	0009-2363	en_US
dc.identifier.uri	http://hdl.handle.net/10453/27638
dc.description.abstract	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.	en_US
dc.relation.ispartof	Chemical and Pharmaceutical Bulletin	en_US
dc.relation.isbasedon	10.1248/cpb.c12-00967	en_US
dc.subject.classification	General Chemistry	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	K562 Cells	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Paclitaxel	en_US
dc.subject.mesh	Vinblastine	en_US
dc.subject.mesh	Doxorubicin	en_US
dc.subject.mesh	ATP Binding Cassette Transporter, Subfamily B, Member 1	en_US
dc.subject.mesh	Antineoplastic Agents	en_US
dc.subject.mesh	Cell Survival	en_US
dc.subject.mesh	Drug Resistance, Neoplasm	en_US
dc.subject.mesh	Heterocyclic Compounds, 4 or More Rings	en_US
dc.title	Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives	en_US
dc.type	Journal Article
utslib.citation.volume	4	en_US
utslib.citation.volume	61	en_US
utslib.for	0304 Medicinal and Biomolecular Chemistry	en_US
utslib.for	0306 Physical Chemistry (incl. Structural)	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CCET - Centre for Clean Energy Technology
utslib.copyright.status	open_access
pubs.issue	4	en_US
pubs.publication-status	Published	en_US
pubs.volume	61	en_US

Abstract:

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.

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http://hdl.handle.net/10453/27638