Inhibition of cell growth and telomerase activity of breast cancer cells in vitro by retinoic acids

The effects of retinoic acid (RA) and its analogs, all-trans RA, 9-cisRA an d 13-cis RA, were investigated in human breast cancer MCF-7 cells and immor talized breast epithelial cell line MCF-10A. RA inhibited the telomerase ac tivity of MCF-7 cells in a wide range of concentrations. RA at 10 mu M also inhibited the growth of MCF-7 cells in a time-dependent manner. However, n o significant growth inhibition was found between untreated control and RA- treated MCF-10A cells. Moreover, a marked inhibition of telomerase activity by RA was detected early in MCF-7 cells (after 24 h of RA treatment), whic h was preceded by a reduction of hTERT mRNA expression (after 12 h of RA tr eatment). However, MCF-10A cells showed a reduction of telomerase activity and down-regulation of hTERT after 4 days of RA treatment. Simultaneous cha nges in hTERT mRNA expression and telomerase activity were found for MCF-10 A cells. The expressions of hTR and hTEP1 telomerase component genes were n ot changed after RA treatment. These results indicate that the anti-breast cancer activity of RA could be mediated by its ability to down-regulate the expression of hTERT telomerase gene.