title: Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin.
abstract: BACKGROUND
  Multidrug resistance is a major problem in the treatment of breast cancer, and a number of studies have attempted to find an efficient strategy with which to overcome it. In this study, we investigate the synergistic anticancer effects of resveratrol (RSV) and doxorubicin (Dox) against human breast cancer cell lines.
  
  
  METHODS
  The synergistic effects of RSV on chemosensitivity were examined in Dox-resistant breast cancer (MCF-7/adr) and MDA-MB-231 cells. In vivo experiments were performed using a nude mouse xenograft model to investigate the combined sensitization effect of RSV and Dox.
  
  
  CONCLUSIONS
  RSV markedly enhanced Dox-induced cytotoxicity in MCF-7/adr and MDA-MB-231 cells. Treatment with a combination of RSV and Dox significantly increased the cellular accumulation of Dox by down-regulating the expression levels of ATP-binding cassette (ABC) transporter genes, MDR1, and MRP1. Further in vivo experiments in the xenograft model revealed that treatment with a combination of RSV and Dox significantly inhibited tumor volume by 60%, relative to the control group.
  
  
  CONCLUSIONS
  These results suggest that treatment with a combination of RSV and Dox would be a helpful strategy for increasing the efficacy of Dox by promoting an intracellular accumulation of Dox and decreasing multi-drug resistance in human breast cancer cells.
authors.affiliation: Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, Busan 609-735, Republic of Korea; Division of Toxicology, College of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Shin
authors.forename: A Jin
authors.initials: AJ
authors.lastname: Won
authors.forename: Byung Mu
authors.initials: BM
authors.lastname: Lee
authors.forename: Wahn Soo
authors.initials: WS
authors.lastname: Choi
authors.forename: Jee H
authors.initials: JH
authors.lastname: Jung
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000008:administration & dosage; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004317:Doxorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D000077185:Resveratrol; D013267:Stilbenes; C513055:ABCB1 protein, human; C421109:multidrug resistance-associated protein 1
keywords: ABC transporter; ATP-binding cassette transporter; Breast cancer; DMEM; DMSO; Dimethylsulfoxide; Dox; Doxorubicin; Doxorubicin-resistant MCF-7; Drug-resistant; Dulbecco's Modified Eagle Medium; MCF-7/adr; MDR; MRP; Multi-drug resistance; Multi-drug resistance associated protein; P-glycoprotein; P-gp; RSV; RT-PCR; Resveratrol; Reverse transcription polymerase chain reaction; TUNEL; Terminal deoxynuclotidyl transferase dUTP nick end labeling