title: [Reversal effect and its mechanism of (- )-5-N-acetylardeemin on adriamycin resistance in multidrug-resistant cancer cells A549/Adr and MCF-7/Adr].
abstract: OBJECTIVE
  To explore the reversal effect of (- )-5-N-acetylardeemin on adriamycin resistance in multidrug-resistant cancer cells including human breast cancer cells MCF-7/Adr and human non-small cell lung cancer cells A549/Adr in vitro.
  
  
  METHODS
  The multidrug-resistant cancer cells MCF-7/Adr, A549/Adr and their respective parental cells were treated with different concentrations of (- )-5-N-acetylardeemin and adriamycin individually or in combination. Cell death was detected based on the release of lactate dehydrogenase (LDH) using a cytotoxicity detection kit. Intracellular accumulation of adriamycin was measured by the detection of fluorescence intensity of cell lysates using microplate reader. The expression of P-glycoprotein (P-gp) was evaluated by Western blot.
  
  
  RESULTS
  (-)-5-N-acetylardeemin significantly reversed the adriamycin resistance in MCF-7/Adr and A549/ Adr in a dose-dependent manner, and the reversal folds were 10. 8 in MCF-7/Adr cells and 20.1 in A549/Adr cells with the treatment of 10 μmol/L (-)-5-N acetylardeemin. (- )-5-N-acetylardeemin also enhanced the sensitivity of parental MCF-7 and A549 cells to adriamycin. The fluorescence intensity in both MCF-7/Adr and A549/Adr cells, which reflected the intracellular accumulation of adriamycin, were significantly enhanced by ( -)5-N- acetylardeemin in a dose-dependent manner. The expressions of P-gp in MCF-7/Adr and A549/Adr cells were significantly inhibited by (- )-5-N-acetylardeemin.
  
  
  CONCLUSIONS
  (- )5-N-acetylardeemin could reverse the multidrug resistance in cancer cells through inhibiting the expression of P-gp and enhancing the intracellular accumulation of cytotoxic drug.
authors.affiliation: Department of Forensic Analytical Toxicology, Sichuan University, Chengdu, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.forename: Xue-lian
authors.initials: XL
authors.lastname: Zheng
authors.forename: You-yi
authors.initials: YY
authors.lastname: Yan
authors.forename: Hao
authors.initials: H
authors.lastname: Song
authors.forename: Dao-xia
authors.initials: DX
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Yong
authors.initials: Y
authors.lastname: Qin
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Lin-chuan
authors.initials: LC
authors.lastname: Liao
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D011744:Pyrimidinones / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D011744:Pyrimidinones; C080891:5-N-acetylardeemin; D004317:Doxorubicin