title: 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 -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.
authors.affiliation: Department of Clinical Pharmacy, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China. xuhongbin119 @ yahoo.cn
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Xu
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Fu
authors.forename: Xia-Ping
authors.initials: XP
authors.lastname: Mao
authors.forename: Lu-Zhong
authors.initials: LZ
authors.lastname: Xu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004317:Doxorubicin; D005978:Glutathione; D005982:Glutathione Transferase; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012717:Sesquiterpenes; D014700:Verapamil; C445979:beta-elemene; C421109:multidrug resistance-associated protein 1