title: Resveratrol enhances mitomycin C-mediated suppression of human colorectal cancer cell proliferation by up-regulation of p21WAF1/CIP1.
abstract: OBJECTIVE
  Studies have shown that natural products could potentially be employed in combination therapies to decrease toxicity to healthy tissues by chemotherapy drugs. No studies however, have investigated the potential modulatory role of resveratrol (RV) on mitomycin C (MMC)-mediated effects on colorectal cancer. The aim of the present study was to investigate the impact of RV on MMC-mediated inhibition of colorectal cancer cell proliferation and to assess the potential mechanisms for such effects.
  
  
  METHODS
  Primary cell lines generated from resected colorectal tumor specimens were treated with RV, MMC or RV+MMC and cell proliferation and gene expression analyses were performed.
  
  
  RESULTS
  Suppression of cell proliferation by RV+MMC was significantly greater than individual treatments. RV+MMC synergistically modulated several genes but the up-regulation of p21(WAF1/CIP1) was several-fold greater.
  
  
  CONCLUSIONS
  The up-regulation of p21(WAF1/CIP1), which inhibits the cell cycle at G0/G1 and G2/M phases, may represent the predominant mechanism for enhancement of MMC-mediated anti-cancer effects by resveratrol.
authors.affiliation: Cancer Treatment Centers of America, Midwestern Regional Medical Center, Zion, IL, U.S.A. Irshad.Ali@ctca-hope.com.
authors.forename: Irshad
authors.initials: I
authors.lastname: Ali
authors.affiliation: Cancer Treatment Centers of America, Midwestern Regional Medical Center, Zion, IL, U.S.A.
authors.forename: Donald P
authors.initials: DP
authors.lastname: Braun
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D016213:Cyclins / Q000235:genetics; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D064246:Mad2 Proteins / Q000235:genetics; D016685:Mitomycin / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000235:genetics; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D015854:Up-Regulation / Q000187:drug effects; D028901:alpha Karyopherins / Q000235:genetics
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D009687:Nuclear Proteins; C402464:SERTAD1 protein, human; D013267:Stilbenes; D015534:Trans-Activators; D014157:Transcription Factors; D028901:alpha Karyopherins; C087978:karyopherin alpha 2; D016685:Mitomycin; D018844:Cyclin-Dependent Kinases; D000077185:Resveratrol
keywords: cell cycle; colorectal cancer; mitomycin C; p21WAF1/CIP1; resveratrol