Mechanisms of arsenic trioxide induced apoptosis of human cervical cancer HeLa cells and protection by Bcl-2

It was recently reported that arsenic trioxide (As2O3) can induce complete remission in patients with acute promyelocytic leukemia (APL). In this pres ent article, the biological effect of As2O3 on human cervical cancer HeLa c ells and HeLa cells overexpressing Bcl-2 is studied. By MIT and colony form ing ability assays, morphology alteration, now cytometric analysis, DNA gel electrophoresis and in situ cell death detection (TUNEL), it was found tha t As2O3 inhibited the growth of HeLa cells and induced G2/M arrest and apop tosis of the cells. RT-PCR, Northern blot, Western blot analysis revealed t hat As2O3 induced HeLa cell apoptosis possibly via decreasing the expressio n of c-myc and viral genes. HeLa cells overexpressing Bcl-2 partly resist A s2O3 induced apoptosis, which might be relative to preventing the cells fro m As2O3 caused G2/M block, downregulation of c-myc gene expression and inhi bition of viral gene expression was also noted. However, it was found that As2O3 at a high concentration could also induce apoptosis of HeLa cells ove rexpressing Bcl-2 possibly mainly via downregulating Bcl-2 expression and s lightly inhibiting viral gene expression.