%0 Journal Article
%T Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids
%A Pornngarm Limtrakul
%A Songyot Anuchapreeda
%A Duang Buddhasukh
%J BMC Cancer
%D 2004
%I BioMed Central
%R 10.1186/1471-2407-4-13
%X In this study, natural curcuminoids, pure curcumin, demethoxycurcumin and bisdemethoxycurcumin, isolated from turmeric (Curcuma longa Linn), were compared for their potential ability to modulate the human MDR-1 gene expression in multidrug resistant human cervical carcinoma cell line, KB-V1 by Western blot analysis and RT-PCR.Western blot analysis and RT-PCR showed that all the three curcuminoids inhibited MDR-1 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 MDR-1 gene expression in a dose dependent manner and had about the same potent inhibitory effect on MDR-1 gene expression as our natural curcuminoid mixtures.These results indicate that bisdemethoxycurcumin is the most active of the curcuminoids present in turmeric for modulation of MDR-1 gene. Treatment of drug resistant KB-V1 cells with curcumin increased their sensitivity to vinblastine, which was consistent with a decreased MDR-1 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.The human MDR-1 gene encoding for MDR transporter (Pgp-170) belongs to ATP-binding cassette (ABC) transporter superfamily. The MDR-1 overexpression has been reported in many tumors and in vitro selected drug-resistant cell lines [1-4]. Uptake and/or efflux of isotope-labelled drugs or rhodamine123 are frequently used for functional assay of Pgp-170 in tumor cells. Several classes of MDR modulators that inhibit Pgp-mediated efflux have been identified. It has been found that the accumulation of chemotherapy agents in tumor cells with overexpressed Pgp-170 was significantly reduced as compared to the MDR a
%K Curcuma longa Linn
%K natural curcuminoids
%K bisdemethoxycurcumin
%K MDR modulators
%K multidrug-resistance
%U http://www.biomedcentral.com/1471-2407/4/13