Effect of Roscovitine and mifepristone in luminal breast cancer cells.

LUCÍA VOTTERO; CLAUDIA LANARI; VICTORIA T FABRIS

Congreso; AACR Virtual Annual Meeting II; 2020

The cyclin dependent kinase (CDK)4/6 inhibitors (Palbociclib, Ribociclib and Abemaciclib) have been recently approved in combination with endocrine therapy for luminal breast cancer treatment. On the other hand, the use of CDK2 inhibitors, such as Roscovitine, appears as a therapeutic alternative to overcome the acquisition of resistance to Palbociclib. However, there are few clinical trials using CDK2 inhibitors for breast cancer treatment. Most of the reports on the effects of Roscovitine were performed in MCF-7 or MDA-MB-231 cells. The aim of this work was to evaluate the effect of Roscovitine on cell proliferation in T47D human breast cancer cells which express both progesterone receptor (PR) isoforms PRA and PRB, and in the T47D-YA and T47D-YB cell lines expressing only PRA or PRB, respectively. We have previously demonstrated that cells overexpressing PRB showed higher levels of cyclin A as compared with those overexpressing PRA, thus we hypothesized that they would be more sensitive to CDK2 inhibitors. Roscovitine inhibited cell proliferation in a dose dependent manner similarly in both MCF-7 cells (used as positive control) and in T47D cells, with IC50 of 11.99 µM and 11.93 µM respectively. In addition, Roscovitine inhibited cell proliferation induced by estrogen treatment in both cell lines (p