title: Genistein suppresses the proliferation of telomerase-negative cells.
abstract: In both tumor and yeast cells that lack telomerase, telomeres are maintained via an alternative recombination mechanism. In this study, we tested genistein, a potential TOP2 inhibitor required for telomere-telomere recombination, on the repression of telomere-telomere recombination. Genistein on the repression of type II recombination on atlc1yeast strain was examined by the telomeric DNA structures using Southern blot analysis. Telomere patterns of freshly dissectedtlc1spores containing an empty plasmid (pYES2) or a yeastTOP2(yTOP2) plasmid were analyzed. The results indicated that the reintroduction ofTOP2recovered the type II pattern, implying genistein in the blockage of type II survivors in thetlc1strain. The effects of genistein on bothtlc1 andtlc1 rad 51strains in liquid and solid mediums were also examined. Finally, treatment of 10μmol/L of genistein showed inhibitory effect on the growth of telomerase-negative U2OS alternative lengthening of telomere (ALT) cells, but not in telomerase-positive HCT116 cells. These results provide evidences that the inhibitory effects of genistein on telomerase-negative cells depend on type II recombination pathway in yeast and the ALT pathway in human tumors.
authors.affiliation: Department of Food Science China University of Science and Technology Taipei 115 Taiwan.
authors.forename: Chuan-Chuan
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Microbiology College of Medicine National Taiwan University Taipei 100 Taiwan.
authors.forename: Meng-Hsun
authors.initials: MH
authors.lastname: Hsieh
authors.affiliation: Department of Microbiology College of Medicine National Taiwan University Taipei 100 Taiwan.
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Teng
keywords: Cancer; genistein; isoflavones; recombination; telomere; topoisomerase II