ROTENONE, A MITOCHONDRIAL NADH DEHYDROGENASE INHIBITOR, INDUCES CELL-SURFACE EXPRESSION OF CD13 AND CD38 AND APOPTOSIS IN HL-60 CELLS

We previously demonstrated that the mitochondrial NADH dehydrogenase s ubunit 2 (ND2) gene was overexpressed in human acute myelogenous leuke mia (AML) cells. Since this finding suggested that ND2 gene expression was related to myeloid differentiation, we here investigated the effe cts of rotenone, a specific NADH dehydrogenase inhibitor, on HL-60 cel l growth, differentiation and death. Fifty nM rotenone inhibited the g rowth of HL-60 cells and caused an increase in the cell population in the G(2) + M phase. In the quantitative comparison of myeloid antigen, the expression of CD13 and CD38 were relatively increased in the rote none-treated cells. These findings suggest that the inhibition of NADH dehydrogenase changes the cell cycle and induces some specific surfac e antigens of HL-60 cells. On the other hand, the expression of ND2 ge ne remained unchanged after the rotenone treatment, suggesting the rot enone-mediated mitochondrial inhibition did not affect the mitochondri al gene expression. Five mu M rotenone strongly inhibited the cellular proliferation. Electron microscopy and an electrophoretic analysis of DNA showed that the majority of the HL-60 cells were induced into typ ical apoptosis within 24-48 hours. On the basis of this and other stud ies, we believe that mitochondrial function is directly involved in bo th cellular differentiation and apoptotic cell death.