Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3

Int J Cancer. 2002 Jun 20;99(6):846-52. doi: 10.1002/ijc.10428.

Abstract

Genistein is a major component of soybean isoflavone and has multiple functions resulting in antitumor effects. Prostate cancer is 1 of the targets for the preventive role of genistein. We examined the effect of genistein on human prostate cancer (LNCaP and PC-3) cells. Proliferation of both cell lines was inhibited by genistein treatment in a dose-dependent manner. To obtain the gene expression profile of genistein in LNCaP cells, we performed cDNA microarray analysis. The expression of many genes, including apoptosis inhibitor (survivin), DNA topoisomerase II, cell division cycle 6 (CDC6) and mitogen-activated protein kinase 6 (MAPK 6), was downregulated. Expression levels were increased more than 2-fold in only 4 genes. The glutathione peroxidase (GPx)-1 gene expression level was the most upregulated. Quantitative real-time polymerase chain reaction revealed significant elevation of transcript levels of GPx-1 in both LNCaP and PC-3 cells. Upregulation of gene expression levels accompanied elevation of GPx enzyme activities. In contrast, no significant changes were observed in the gene expression levels and enzyme activities of the other antioxidant enzymes, superoxide dismutase and catalase. GPx activation might be one of the important characteristics of the effects of genistein on prostate cancer cells.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Catalase / biosynthesis
  • Catalase / genetics
  • Cell Division / drug effects
  • DNA Primers / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Gene Expression Profiling
  • Genistein / pharmacology*
  • Glutathione Peroxidase / biosynthesis*
  • Glutathione Peroxidase / genetics
  • Glycine max / chemistry
  • Humans
  • Isoflavones / pharmacology
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / enzymology
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species
  • Superoxide Dismutase / biosynthesis
  • Superoxide Dismutase / genetics
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / enzymology
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • DNA Primers
  • Enzyme Inhibitors
  • Isoflavones
  • RNA, Messenger
  • Reactive Oxygen Species
  • Genistein
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase