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  • Reversion of P-glycoprotein-mediated multidrug resistance by guggulsterone in multidrug-resistant human cancer cell lines.

Reversion of P-glycoprotein-mediated multidrug resistance by guggulsterone in multidrug-resistant human cancer cell lines.

European journal of pharmacology (2012-09-11)
Hong-Bin Xu, Lu-Zhong Xu, Ling Li, Jun Fu, Xia-Ping Mao
ABSTRACT

Multidrug resistance (MDR) presents a serious problem in cancer chemotherapy. Our previous studies have shown that guggulsterone could reverse MDR through inhibiting the function and expression of P-glycoprotein (P-gp). The present study is to further investigate the reversal effects of guggulsterone on MDR in drug-resistant cancer cell lines. The effects of guggulsterone on MDR1mRNA gene expression, intracellular pH, P-gp ATPase activity and glucosylceramide synthase (GCS) expression were assessed by RT-PCR, Laser Scanning Confocal Microscope using the pH-sensitive fluorescent probe BCECF-AM, Pgp-Glo assay system, and flow cytometric technology, respectively. The results showed that guggulsterone ranging from 2.5 to 80 μM significantly promoted the activity of P-gp ATPase in a dose-dependent manner. The intracellular pH of K562/DOX cells was found to be higher than K562 cells. After treatment with guggulsterone (1, 3, 10, 30, 100 μM), intracellular pH of K562/DOX cells decreased in a dose- and time-dependent manner. However, the present study revealed that guggulsterone ranging from 3 to 100 μM had little influence on MDR1 gene expression in K562/DOX cells. Further, the isogenic doxorubicin-resistant MCF-7/DOX cells exhibited a 4.9-fold increase in GCS level as compared with parental MCF-7 human breast cancer cells. After treatment with guggulsterone (0.1, 1, 10 μM) for 48 h, MCF-7/DOX cells were found to have no change of GCS protein expression amount. Guggulsterone might be a potent MDR reversal agent, and its mechanism on MDR needs more research.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
(Z)-Guggulsterone, ≥89% (HPLC), powder
Pricing and availability is not currently available.
Sigma-Aldrich
(E)-Guggulsterone, ≥95% (HPLC), powder
Pricing and availability is not currently available.