Specific reversal of multidrug resistance to colchicine in CEM/VLB<inf>100</inf> cells by Gynostemma pentaphyllum extract
- Publication Type:
- Journal Article
- Citation:
- Phytomedicine, 2007, 14 (12), pp. 830 - 839
- Issue Date:
- 2007-12-04
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P-glycoprotein (P-gp)-mediated multiple drug resistance (MDR) is perhaps the most thoroughly studied cellular mechanism of cytotoxic drug resistance. Its efflux function can be circumvented by a wide range of pharmacological agents in vitro and in vivo. Most of these agents are pharmaceuticals used clinically for conditions other than cancer. However, their use in alleviating MDR is limited because the concentrations required for inhibition of the pump surpass their dose-limiting toxicity. The aim of this research is to study the role of gypenosides, isolated from Gynostemma pentaphyllum, as modulators of P-gp-mediated MDR in tumor cells, at both cellular and plasma membrane level. In the presence of total gypenoside preparation (0.1 mg/ml), an approximately 15-fold reversal of colchicine (COL) resistance was observed in P-gp-overexpressed CEM/VLB100 cells. However, the gypenoside sample showed no reversal effect in cells treated with vinblastine and taxol. A purified gypenoside sample (gypenoside fraction 100) exhibited even more significant reversal of COL resistance (∼42-fold) in the CEM/VLB100 cells. Further examination of the reversal effect of fraction 100 in membrane vesicles derived from CEM/VLB100 cells using the continuous fluorescence method found that gypenoside fraction 100 at 0.1 mg/ml completely abolished the transport of fluorescein-COL. © 2007 Elsevier GmbH. All rights reserved.
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