Genistein suppresses the proliferation of telomerase-negative cells.

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 a tlc1 yeast strain was examined by the telomeric DNA structures using Southern blot analysis. Telomere patterns of freshly dissected tlc1 spores containing an empty plasmid (pYES2) or a yeast TOP2 (yTOP2) plasmid were analyzed. The results indicated that the reintroduction of TOP2 recovered the type II pattern, implying genistein in the blockage of type II survivors in the tlc1 strain. The effects of genistein on both tlc1 and tlc1 rad 51 strains in liquid and solid mediums were also examined. Finally, treatment of 10 µmol/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.