We reported recently that
roscovitine (ROSC), a selective
cyclin-dependent kinase (CDK) inhibitor, arrested human MCF-7
breast cancer cells in G2 phase of the cell cycle and concomitantly induced apoptosis. On the other hand, ROSC-induced G1 arrest observed by another group has not been accompanied by apoptosis. Therefore, we decided to prove to which extent components of tissue
culture media could affect the primary action of ROSC. For this purpose we compared the efficacy of the ROSC treatment on MCF-7 cells cultivated in medium with and without
phenol red. The kinetics of MCF-7 cell proliferation strongly depended on the presence of
phenol red that has been recognized previously as a weak
estrogen. Exposure of MCF-7 cells cultivated in
phenol red-deprived medium to ROSC resulted in a strong G2 arrest and apoptosis. However, the anti-proliferative and pro-apoptotic action of ROSC was strongly diminished in cells maintained in medium containing
phenol red. The ratio of the G2 cell population after 12 h ROSC was reduced by approximately 20% in the latter and correlated with the lack of CDK2 inactivation. Moreover, the kinetics of ROSC-induced apoptosis was delayed in the presence of
phenol red. These results clearly evidence that the efficacy of the
therapy of ER-positive breast
cancers by CDK inhibitors is diminished in the presence of
estrogen-mimicking compounds and indicate that
phytoestrogens and xenoestrogens could interfere with the
therapy. Therefore, the exposure of
cancer patients to the
estrogen mimics should be avoided at least during
chemotherapy by CDK inhibitors.