title: Increase in apoptosis by combination of metformin with silibinin in human colorectal cancer cells.
abstract: OBJECTIVE
  To investigate the effect of metformin on silibinin-induced apoptosis in human colorectal cancer (COLO 205) cells.
  
  
  METHODS
  MTT assays were performed to quantify cell viability. Western blot assays were applied to identify the expression of signaling proteins.
  
  
  RESULTS
  The combined treatment of COLO 205 cells with metformin and silibinin decreased cell survival at a dose insufficient to influence the non-malignant cells [Human colonic epithelial cells (HCoEpiC)]. Silibinin and metformin increased phosphatase and tensin homolog and 5'-adenosine monophosphate-activated protein kinase expression in COLO 205 cells and inhibited the phosphorylation of mammol/Lalian target of rapamycin. This combined treatment resulted in an increase in the expression of activated caspase 3 and apoptosis inducing factor, indicating apoptosis.
  
  
  CONCLUSIONS
  The combined treatment of human colorectal cancer cells with silibinin and metformin may induce apoptosis at a dose that does not affect HCoEpiC. This finding reveals a potential therapeutic strategy for the treatment of colorectal cancer.
authors.affiliation: Cheng-Chia Tsai, Department of Surgery, Mackay Memorial Hospital, Taipei City 10401, Taiwan.
authors.forename: Cheng-Chia
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: Cheng-Chia Tsai, Department of Surgery, Mackay Memorial Hospital, Taipei City 10401, Taiwan.
authors.forename: Tang-Wei
authors.initials: TW
authors.lastname: Chuang
authors.affiliation: Cheng-Chia Tsai, Department of Surgery, Mackay Memorial Hospital, Taipei City 10401, Taiwan.
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Chen
authors.affiliation: Cheng-Chia Tsai, Department of Surgery, Mackay Memorial Hospital, Taipei City 10401, Taiwan.
authors.forename: Ho-Shan
authors.initials: HS
authors.lastname: Niu
authors.affiliation: Cheng-Chia Tsai, Department of Surgery, Mackay Memorial Hospital, Taipei City 10401, Taiwan.
authors.forename: Kun-Ming
authors.initials: KM
authors.lastname: Chung
authors.affiliation: Cheng-Chia Tsai, Department of Surgery, Mackay Memorial Hospital, Taipei City 10401, Taiwan.
authors.forename: Juei-Tang
authors.initials: JT
authors.lastname: Cheng
authors.affiliation: Cheng-Chia Tsai, Department of Surgery, Mackay Memorial Hospital, Taipei City 10401, Taiwan.
authors.forename: Kao-Chang
authors.initials: KC
authors.lastname: Lin
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D008687:Metformin / Q000494:pharmacology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D012838:Silymarin; D000077385:Silybin; D008687:Metformin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Apoptosis; COLO 205; Colorectal cancer; Mammol/Lalian target of rapamycin; Metformin; Silibinin