Phenol red reduces ROSC mediated cell cycle arrest and apoptosis in human MCF-7 cells.

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. (c) 2006 Wiley-Liss, Inc.