title: The relationship between anticancer effect of metformin and the transcriptional regulation of certain genes (CHOP, CAV-1, HO-1, SGK-1 and Par-4) on MCF-7 cell line.
abstract: BACKGROUND
  1,1-dimethylbiguanide hydrochloride (biguanide metformin) is a hypoglycemic agent that is widely used in the treatment of Type 2 diabetes. Use of metformin was found to be associated with the lower risk of cancer. It is suggested that metformin has an anticancer and antiproliferative effect and affects the apoptosis by activating the AMPK and inhibiting the mammalian target of rapamycin (mTOR). Although the effects of metformin treatment of various types of cancers are defined with many mechanisms, the literature provides only sufficient information about how it affects the SGK-1, Par-4 and Cav-1 mRNA expressions and the impact of this effect on cytotoxicity. The breast cancer is globally one of the most important causes of cancer-related mortality for women. We, therefore investigated the possible effects of metmorfin on proliferation, cytotoxicity and some unfolded protein response (UPR) genes in the breast cancer cells (MCF-7).
  
  
  METHODS
  We administrated 0.31 mM, 2.5 mM and 10 mM of metformin alone and in combination with 2-DG to the MCF-7 cells and monitored the cell viability and proliferation with real-time cell analyzer system for 48 hours. We also measured CHOP, Cav-1, HO-1, SGK-1 and Par-4 genes mRNA expression levels using Real Time-Polymerase Chain Reaction (RT-PCR). We considered the GAPDH gene as reference gene and the control groups as calibrator. We performed an analysis for relative gene expressions of the study groups.
  
  
  RESULTS
  Metformin caused transcriptional regulation of UPR and tumor-related genes in MCF-7 cells and inhibited the proliferation depending on the dose, resulting in cytotoxic effect.
  
  
  CONCLUSIONS
  We consider that administration of metformin with chemotherapeutic agents could be an effective method in treatment of breast cancer through mechanisms such as reduced resistance to chemotherapy and increased cytotoxic activity.
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey. dr.osmansalis@hotmail.
authors.forename: O
authors.initials: O
authors.lastname: Salis
authors.forename: A
authors.initials: A
authors.lastname: Bedir
authors.forename: T
authors.initials: T
authors.lastname: Ozdemir
authors.forename: A
authors.initials: A
authors.lastname: Okuyucu
authors.forename: H
authors.initials: H
authors.lastname: Alacam
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D051242:Caveolin 1 / Q000096:biosynthesis / Q000235:genetics; D003847:Deoxyglucose / Q000008:administration & dosage; D005260:Female; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics; D061986:MCF-7 Cells; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051742:Transcription Factor CHOP / Q000096:biosynthesis / Q000235:genetics; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D051242:Caveolin 1; D003847:Deoxyglucose; D051547:Heme Oxygenase-1; D017874:Immediate-Early Proteins; D008687:Metformin; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D051742:Transcription Factor CHOP; D000099184:Serum-Glucocorticoid Regulated Kinases; C495540:CAV1 protein, human; C497249:DDIT3 protein, human; C101296:prostate apoptosis response-4 protein; C496541:HMOX1 protein, human