ABSTRACT
The use of histone deacetylase inhibitors and inhibitors of MEK/ERK-pathway is proposed as a novel potential approach in cancer treatment. Here we studied the effects of histone deacetylase inhibitor, sodium butyrate, and MEK/ERK-pathway inhibitor, PD0325901, on cells with modifications in genes involved in anti-cancer therapy response, Wip1 phosphatase and p53. We have investigated the effect of these agents on cell cycle of wild-type cells, Wip1 knockout cells and cells with double deletion of Wip1 and p53. Our results showed that more severe changes in S and G2/M phases were observed in response to sodium butyrate in Wip1-defecient cells than in wild-type cells. Meanwhile, PD0325901 treatment led to G1 arrest. At the same time, a «sodium butyrate type¼ response dominated the response to combined treatment with both drugs in Wip1-deficient cells, while the response of Wip1//p53/ cells to combined treatment was similar to the single use of PD0325901. Wip1/ and Wip1//p53/ cells were more sensitive to the use of PD0325901 than wild-type cells. Obtained results suggest that Wip1 deficiency sensitizes cells to sodium butyrate and to MEK/ERK inhibitors independently from Wip1 main target protein p53. Data acquired give insights into role of Wip1 in cellular responses to treatment with HDAC and MEK/ERK inhibitors.
