The effect of three anticancer drugs (Bortezomib,Paclitaxel and Lapatinib) on stemness and aneuploidy rate in human embryonic stem cells

Aneuploidies following in vitro culture is one of the challenges for application of human embryonic stem cells (hESCs). There are reports that indicate more sensitivity of aneuploid cells to some anticancer drugs and probability of reduction of aneuploidy rate.Mosaic hESCs was obtained by mixing of normal hESCs and trisomic hESCs for chromosomes 12 and 17. The effect of 3 anticancer drugs, Bortezomib, Paclitaxel (Taxol) and Lapatinib on chromosomal status was studied by karyotyping. Stemness characterization was performed using alkaline phosphatase test and expression analysis of pluripotency genes using Real Time PCR. All treated groups were compared with controls. When cells treated with 0.01 μM of Bortezomib and 0.2 μM of Lapatinib for 24 hours, there was no significant difference between treated and the control groups. Paclitaxel treatment for 28 hours showed the most viability with no significant difference from control whilst shorter and longer exposure periods were cytotoxic. Treated and control groups did not have significant difference in karyotype and pluripotency genes expression. Aneuploid cells became dominant population in all of treated and control groups. All treated groups were alkaline phosphatase-positive.Mentioned treatments did not affect pluripotency. Insensitivity of aneuploid cells to treated anticancer drugs could be due to specific characters of each cell line and proliferation dominance of cells with trisomies 12 and 17.