title: Genistein potentiates the effect of 17-beta estradiol on human hepatocellular carcinoma cell line.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. This cancer may be due to a multistep process with an accumulation of epigenetic alterations in tumor suppressor genes (TSGs), leading to hypermethylation of the genes. Hypermethylation of TSGs is associated with silencing and inactivation of them. It is well-known that DNA hypomethylation is the initial epigenetic abnormality recognized in human tumors. Estrogen receptor alpha (ERα) is one of the TSGs which modulates gene transcription and its hypermethylation is because of overactivity of DNA methyltransferases. Fortunately, epigenetic changes especially hypermethylation can be reversed by pharmacological compounds such as genistein (GE) and 17-beta estradiol (E2) which involve in preventing the development of certain cancers by maintaining a protective DNA methylation. The aim of the present study was to analyze the effects of GE on ERα and DNMT1 genes expression and also apoptotic and antiproliferative effects of GE and E2 on HCC.
  
  
  METHODS
  Cells were treated with various concentrations of GE and E2 and the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay was used. Furthermore, cells were treated with single dose of GE and E2 (25 μM) and flow cytometry assay was performed. The expression level of the genes was determined by quantitative real-time reverse transcription polymerase chain reaction.
  
  
  RESULTS
  GE increased ERα and decreased DNMT1 genes expression, GE and E2 inhibited cell viability and induced apoptosis significantly.
  
  
  CONCLUSIONS
  GE can epigenetically increase ERα expression by inhibition of DNMT1 expression which in turn increases apoptotic effect of E2. Furthermore, a combination of GE and E2 can induce apoptosis more significantly.
authors.affiliation: Department of Anatomical Sciences, Medical School, Jahrom University of Medical Sciences, Jahrom, Iran.
authors.forename: Fraidoon
authors.initials: F
authors.lastname: Kavoosi
authors.affiliation: Department of Anatomical Sciences and Molecular Biology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mehdi Nikbakht
authors.initials: MN
authors.lastname: Dastjerdi
authors.affiliation: Department of Anatomical Sciences and Molecular Biology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Valiani
authors.affiliation: Department of Anatomical Sciences and Molecular Biology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Esfandiari
authors.affiliation: Department of Anatomical Sciences, Medical School, Jahrom University of Medical Sciences, Jahrom, Iran.
authors.forename: Masumeh
authors.initials: M
authors.lastname: Sanaei
authors.affiliation: Cellular and Molecular Immunology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mazdak Ganjalikhani
authors.initials: MG
authors.lastname: Hakemi
keywords: DNMT1; E2; epigenetic; estrogen receptor alpha; genistein; hepatocellular carcinoma