Hong-Bin Xu1, Ling Li, Jun Fu, Xia-Ping Mao, Lu-Zhong Xu. 1. Department of Clinical Pharmacy, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China. xuhongbin119 @ yahoo.cn
Abstract
BACKGROUND: Multidrug resistance (MDR) presents a problem in cancer chemotherapy, and developing new agents to overcome MDR is important. This study intends to investigate the reversal effect of -elemene on MDR in human breast carcinoma MCF-7 and doxorubicin-resistant MCF-7 cells. METHODS: MTT cytotoxicity assays, flow cytometry, and Western blot analysis were performed to investigate the antiproliferative effects of the combination of anticancer drugs with -elemene, to study the reversal of drug resistance, and to examine the inhibitory effects on protein expression. RESULTS: The results showed that -elemene (30 μ mol/l) had a strong potency to increase the cytotoxicity of doxorubicin to MCF-7/DOX cells, with a reversal fold of 6.38. In addition, the mechanisms of -elemene in reversing P-glycoprotein (Pgp)-mediated MDR demonstrated that -elemene significantly increases the intracellular accumulations of doxorubicin and Rh123 via inhibition of the P-gp transport function in MCF-7/DOX cells. Flow cytometry and Western blot analyses revealed that -elemene could inhibit the expression of P-gp, while it had little effect on the expression of MRP1 protein. In addition, -elemene had little inhibitory effect on the intracellular GSH levels and GST activities in MCF-7/DOX cells. CONCLUSIONS: -Elemene might represent a promising agent for overcoming MDR in cancer therapy.
BACKGROUND: Multidrug resistance (MDR) presents a problem in cancer chemotherapy, and developing new agents to overcome MDR is important. This study intends to investigate the reversal effect of -elemene on MDR in humanbreast carcinoma MCF-7 and doxorubicin-resistant MCF-7 cells. METHODS:MTTcytotoxicity assays, flow cytometry, and Western blot analysis were performed to investigate the antiproliferative effects of the combination of anticancer drugs with -elemene, to study the reversal of drug resistance, and to examine the inhibitory effects on protein expression. RESULTS: The results showed that -elemene (30 μ mol/l) had a strong potency to increase the cytotoxicity of doxorubicin to MCF-7/DOX cells, with a reversal fold of 6.38. In addition, the mechanisms of -elemene in reversing P-glycoprotein (Pgp)-mediated MDR demonstrated that -elemene significantly increases the intracellular accumulations of doxorubicin and Rh123 via inhibition of the P-gp transport function in MCF-7/DOX cells. Flow cytometry and Western blot analyses revealed that -elemene could inhibit the expression of P-gp, while it had little effect on the expression of MRP1 protein. In addition, -elemene had little inhibitory effect on the intracellular GSH levels and GST activities in MCF-7/DOX cells. CONCLUSIONS:-Elemene might represent a promising agent for overcoming MDR in cancer therapy.
Authors: Muhammad Naeem; Muhammad Omer Iqbal; Humaira Khan; Muhammad Masood Ahmed; Muhammad Farooq; Muhammad Moeen Aadil; Mohamad Ikhwan Jamaludin; Abu Hazafa; Wan-Chi Tsai Journal: Molecules Date: 2022-05-25 Impact factor: 4.927
Authors: Khalid O Alfarouk; Christian-Martin Stock; Sophie Taylor; Megan Walsh; Abdel Khalig Muddathir; Daniel Verduzco; Adil H H Bashir; Osama Y Mohammed; Gamal O Elhassan; Salvador Harguindey; Stephan J Reshkin; Muntaser E Ibrahim; Cyril Rauch Journal: Cancer Cell Int Date: 2015-07-15 Impact factor: 5.722