title: Curcumin enhanced antiproliferative effect of mitomycin C in human breast cancer MCF-7 cells in vitro and in vivo.
abstract: OBJECTIVE
  To investigate the efficacy of mitomycin C (MMC) in combination with curcumin in suppressing human breast cancer in vitro and in vivo.
  
  
  METHODS
  Human breast cancer MCF-7 cells were used. Cell viability was measured using MTT assay. The cell cycle phase was detected with flow cytometric analysis. Cell cycle-associated proteins were examined using Western blot analysis. MCF-7 breast cancer xenografts were established to monitor tumor growth and cell cycle-associated protein expression.
  
  
  RESULTS
  Curcumin inhibited MCF-7 breast cancer cell viability in a concentration-dependent manner (IC(50) value=40 μmol/L). Similarly, MMC inhibited the cell viability with an IC(50) value of 5 μmol/L. Combined treatment of MMC and curcumin showed a synergistic antiproliferative effect. In the presence of curcumin (40 μmol/L), the IC(50) value of MMC was reduced to 5 μmol/L. In MCF-7 xenografts, combined administration of curcumin (100 mg/kg) and MMC (1-2 mg/kg) for 4 weeks produced significantly greater inhibition on tumor growth than either treatment alone. The combined treatment resulted in significantly greater G(1) arrest than MMC or curcumin alone. Moreover, the cell cycle arrest was associated with inhibition of cyclin D1, cyclin E, cyclin A, cyclin-dependent kinase 2 (CDK2) and CDK4, along with the induction of the cell cycle inhibitor p21 and p27 both in MCF-7 cells and in MCF-7 xenografts. These proteins were regulated through p38 MAPK pathway.
  
  
  CONCLUSIONS
  The results suggest that the combination of MMC and curcumin inhibits MCF-7 cell proliferation and cell cycle progression in vitro and in vivo via the p38 MAPK pathway.
authors: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, China.
authors: Qian-mei
authors: QM
authors: Zhou
authors: Xiu-feng
authors: XF
authors: Wang
authors: Xin-jun
authors: XJ
authors: Liu
authors: Hui
authors: H
authors: Zhang
authors: Yi-yu
authors: YY
authors: Lu
authors: Shi-bing
authors: SB
authors: Su
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001940:Breast / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D019938:Cyclin D1 / Q000235:genetics; D019927:Cyclin E / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D019927:Cyclin E; D019938:Cyclin D1; D016685:Mitomycin; D051357:Cyclin-Dependent Kinase 2; D003474:Curcumin