Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids
<p>Abstract</p> <p>Background</p> <p>Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in patient's tumor cells resulting from enhanced drug efflux. It is related to the overexpression of a membrane p...
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| Format: | Article |
| Language: | English |
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BMC
2004-04-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://www.biomedcentral.com/1471-2407/4/13 |
| _version_ | 1818556605913890816 |
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| author | Buddhasukh Duang Anuchapreeda Songyot Limtrakul Pornngarm |
| author_facet | Buddhasukh Duang Anuchapreeda Songyot Limtrakul Pornngarm |
| author_sort | Buddhasukh Duang |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in patient's tumor cells resulting from enhanced drug efflux. It is related to the overexpression of a membrane protein, P-glycoprotein (Pgp-170), thereby reducing drug cytotoxicity. A variety of studies have tried to find MDR modulators which increase drug accumulation in cancer cells.</p> <p>Methods</p> <p>In this study, natural curcuminoids, pure curcumin, demethoxycurcumin and bisdemethoxycurcumin, isolated from turmeric (<it>Curcuma longa </it>Linn), were compared for their potential ability to modulate the human <it>MDR-1 </it>gene expression in multidrug resistant human cervical carcinoma cell line, KB-V1 by Western blot analysis and RT-PCR.</p> <p>Results</p> <p>Western blot analysis and RT-PCR showed that all the three curcuminoids inhibited <it>MDR-1 </it>gene expression, and bisdemethoxycurcumin produced maximum effect. In additional studies we found that commercial grade curcuminoid (approximately 77% curcumin, 17% demethoxycurcumin and 3% bisdemthoxycurcumin) decreased <it>MDR-1 </it>gene expression in a dose dependent manner and had about the same potent inhibitory effect on <it>MDR-1 </it>gene expression as our natural curcuminoid mixtures.</p> <p>Conclusion</p> <p>These results indicate that bisdemethoxycurcumin is the most active of the curcuminoids present in turmeric for modulation of <it>MDR-1 </it>gene. Treatment of drug resistant KB-V1 cells with curcumin increased their sensitivity to vinblastine, which was consistent with a decreased <it>MDR-1 </it>gene product, a P-glycoprotein, on the cell plasma membrane. Although many drugs that prevent the P-glycoprotein function have been reported, this report describes the inhibition of MDR-1 expression by a phytochemical. The modulation of MDR-1 expression may be an attractive target for new chemosensitizing agents.</p> |
| first_indexed | 2024-12-13T23:49:25Z |
| format | Article |
| id | doaj.art-7a5afbc1d8ac42db94049a8e95e5d743 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-13T23:49:25Z |
| publishDate | 2004-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-7a5afbc1d8ac42db94049a8e95e5d7432022-12-21T23:26:50ZengBMCBMC Cancer1471-24072004-04-01411310.1186/1471-2407-4-13Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoidsBuddhasukh DuangAnuchapreeda SongyotLimtrakul Pornngarm<p>Abstract</p> <p>Background</p> <p>Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in patient's tumor cells resulting from enhanced drug efflux. It is related to the overexpression of a membrane protein, P-glycoprotein (Pgp-170), thereby reducing drug cytotoxicity. A variety of studies have tried to find MDR modulators which increase drug accumulation in cancer cells.</p> <p>Methods</p> <p>In this study, natural curcuminoids, pure curcumin, demethoxycurcumin and bisdemethoxycurcumin, isolated from turmeric (<it>Curcuma longa </it>Linn), were compared for their potential ability to modulate the human <it>MDR-1 </it>gene expression in multidrug resistant human cervical carcinoma cell line, KB-V1 by Western blot analysis and RT-PCR.</p> <p>Results</p> <p>Western blot analysis and RT-PCR showed that all the three curcuminoids inhibited <it>MDR-1 </it>gene expression, and bisdemethoxycurcumin produced maximum effect. In additional studies we found that commercial grade curcuminoid (approximately 77% curcumin, 17% demethoxycurcumin and 3% bisdemthoxycurcumin) decreased <it>MDR-1 </it>gene expression in a dose dependent manner and had about the same potent inhibitory effect on <it>MDR-1 </it>gene expression as our natural curcuminoid mixtures.</p> <p>Conclusion</p> <p>These results indicate that bisdemethoxycurcumin is the most active of the curcuminoids present in turmeric for modulation of <it>MDR-1 </it>gene. Treatment of drug resistant KB-V1 cells with curcumin increased their sensitivity to vinblastine, which was consistent with a decreased <it>MDR-1 </it>gene product, a P-glycoprotein, on the cell plasma membrane. Although many drugs that prevent the P-glycoprotein function have been reported, this report describes the inhibition of MDR-1 expression by a phytochemical. The modulation of MDR-1 expression may be an attractive target for new chemosensitizing agents.</p>http://www.biomedcentral.com/1471-2407/4/13<it>Curcuma longa </it>Linnnatural curcuminoidsbisdemethoxycurcuminMDR modulatorsmultidrug-resistance |
| spellingShingle | Buddhasukh Duang Anuchapreeda Songyot Limtrakul Pornngarm Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids BMC Cancer <it>Curcuma longa </it>Linn natural curcuminoids bisdemethoxycurcumin MDR modulators multidrug-resistance |
| title | Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids |
| title_full | Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids |
| title_fullStr | Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids |
| title_full_unstemmed | Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids |
| title_short | Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids |
| title_sort | modulation of human multidrug resistance mdr 1 gene by natural curcuminoids |
| topic | <it>Curcuma longa </it>Linn natural curcuminoids bisdemethoxycurcumin MDR modulators multidrug-resistance |
| url | http://www.biomedcentral.com/1471-2407/4/13 |
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