Reversion of Multidrug Resistance in a Chemoresistant Human Breast Cancer Cell Line by β-Elemene

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 β-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 β-elemene, to study the reversal of drug resistance, and to examine the inhibitory effects on protein expression. Results: The results showed that β-elemene (30 µmol/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 β-elemene in reversing P-glycoprotein (P-gp)-mediated MDR demonstrated that β-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 β-elemene could inhibit the expression of P-gp, while it had little effect on the expression of MRP1 protein. In addition, β-elemene had little inhibitory effect on the intracellular GSH levels and GST activities in MCF-7/DOX cells. Conclusions: β-Elemene might represent a promising agent for overcoming MDR in cancer therapy.

Chemical composition and anticancer activity of essential oils of Mediterranean sage (Salvia officinalis L.) grown in different environmental conditions

“…b-elemene is a broad-spectrum antitumor agent. Several studies have indicated that this compound enhances the cytotoxic effect of radiation in vitro and in vivo (Li et al, 2011); in addition it has been reported that it is able to induce apoptosis in human nonsmall-cell lung cancer A549 cells (Liu et al, 2012), and that might represent a promising agent for overcoming MDR in cancer therapy (Xu et al, 2012). a-Humulene was found active against the prostate cancer cells LNCaP (Tundis et al, 2009).…”

�-Elemene Reverses Chemoresistance of Breast Cancer via Regulating MDR-Related MicroRNA Expression

“…The extract of elemene is a mixture of β, δ and γ-elemene, with β-elemene as the main component, accounting for 60-72% of the three isoforms. Previous studies have provided abundant evidence to reveal that β-elemene might be an effective MDR reversing agent in cancer chemotherapy and mainly via inhibition of the transport activity of Pgp [3,4]. However the underline mechanism has not been fully elucidated.…”

Anticancer effects of β-elemene in gastric cancer cells and its potential underlying proteins: A proteomic study

“…Moreover, BTF has been shown to inhibit DNA damage repair (25,27). This may partly contribute to the fact that β-elemene enhances tumor chemosensitivity or overcomes drug resistance (17,18). The other molecule, Bcl-rambo, is also a pro-apoptotic member of the Bcl-2 family (28,29).…”

“…In recent studies, β-elemene was shown to have diverse anticancer potential, such as inhibiting proliferation and inducing apoptosis of cancer cells, and interacting with multiple oncogenic or tumor suppressing signaling pathways in a broad spectrum of cancers (14)(15)(16). Other studies found that β-elemene could enhance tumor chemosensitivity or overcome drug resistance (17,18). In addition, β-elemene has been approved by the China Food and Drug Administration as a therapeutic drug in clinical practice where its efficacy has been exhibited when combined with first-line chemotherapy for malignant tumors (19,20).…”