Biochemical and Biophysical Research Communications
Reversal of multidrug resistance by 4-chloro-N-(3-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)phenyl)benzamide through the reversible inhibition of P-glycoprotein
Section snippets
Materials and methods
Cell culture. P-gp non-expressing KB cells and P-gp expressing KBV20C cells were cultured in RPMI 1640 (Invitrogen, Carlsbad, CA) with 10% fetal bovine serum (FBS; HyClone Laboratories, Logan, UT) and 1% penicillin/streptomycin (Invitrogen). KBV20C cells were grown in the presence of 20 nM vincristine (Sigma Chemical, St. Louis, MO) as described previously [22].
Reagents and cytotoxicity test. Paclitaxel, verapamil, and rhodamine 123 (Rh123) were obtained from Sigma. Compound C-4 (4-chloro-N-(3-((
C-4 treatment increases vincristine- or paclitaxel-induced cytotoxicity in drug-resistant KBV20C cells
In order to explore the molecular mechanism for the MDR modulating activity of curcumin and its analog C-4, we used P-gp expressing KBV20C cells and its parental line of P-gp non-expressing KB cells. We first determined the cytotoxic response of both KBV20C and KB cells to vincristine or paclitaxel. As expected, KBV20C cells were more resistant than KB cells to paclitaxel and vincristine; IC50 in KB cells were 4.2 nM (paclitaxel) and 7.9 nM (vincristine) (data not shown), whereas those in KBV20C
Discussion
Chemotherapy is the most effective treatment for patients who suffer from metastatic cancers. The effectiveness of chemotherapy, however, is seriously limited by MDR which is mainly due to the overexpression of P-gp, an integral membrane protein. P-gp functions as a drug efflux pump which actively transports drugs from the inside to the outside of cancer cells and prevents the intracellular accumulation of anticancer drugs inside cancer cells necessary for cytotoxic activity. Therefore, novel
Acknowledgments
This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2006-003-E00024, to Y.K. Kim).
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