Mechanism of Thalidomide Induced Apoptosis and DNA Damage in Acute Myeloid Leukemia THP1 Cells
HE Xu, HU Yinshan, YANG Kun, MA Chunrong*
This study investigated the inducing effect and molecular mechanism of thalidomide on apoptosis and DNA damage of acute myeloid leukemia THP1 cells. Taking human acute myeloid leukemia THP1 cells cultured in vitro as the research object, thalidomide with different concentrations (50, 100, 150, 200, 250 μg/mL) was added to the experimental group, and an equal volume of DMSO (dimethyl sulfoxide) was added to the control group. After processing, the inhibitory effect of thalidomide on cell proliferation was detected by CCK-8; the inducing effect of drugs on apoptosis was detected by Calcein/PI method; the changes of mitochondrial membrane potential were detected by JC-1 fluorescence staining; the cell cycle was detected by flow cytometry; the level of mitochondrial cytochrome C protein, apoptosis-related proteins (cleaved-caspase-3 and Bax) and DNA damage related proteins (pATM and γH2AX) were detected by Western blot. The results showed that compared with the control group, the thalidomide of experimental group significantly inhibited the growth of THP1 cells (P<0.05); the inducing effect of thalidomide on apoptosis was concentration dependent; thalidomide decreased mitochondrial membrane potential (P<0.05) and promoted the release of cytochrome C protein from mitochondria; thalidomide induced the G2/M phase arrest of THP1 cells; thalidomide enhanced the expression of apoptosis-related proteins (cleaved-caspase-3 and Bax) and DNA damage response-related proteins (pATM and γH2AX) (P<0.05). These results suggest that thalidomide can induce apoptosis of acute myeloid leukemia THP1 cells, and its mechanism may be related to activating the mitochondrial apoptosis pathway and inducing DNA damage.
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