Therapeutic effect of arsenic trioxide (As2O3) on cervical cancer in vitro and in vivo through apoptosis induction

Arsenic trioxide (As2O3) induces apoptosis in certain types of cancer cells. But the detailed mechanisms of As2O3 efficacy are not completely known. Here we demonstrate that As2O3 has a therapeutic effect on cervical cancer in vitro and in vivo. We investigated the As2O3-induced apoptosis in various cervical cancer cells. The apoptosis was triggered by mitochondrial pathway and associated with dissociation of Bcl-2 from Bax and VDAC, then the release of cytochrome c from Bax and VDAC channel, resulting in the activation of caspase-9 and caspase-3. The overexpression of Bcl-2 counteracted the As2O3- mediated apoptosis. The As2O3 treatment also resulted in an increased M phase cell cycle distribution by inducing microtubule polymerization. Two independent death- signaling pathways in cervical cancer cells were activated, one dominated by JNK/ p38/ GADD45 and one by p53 signals. Further investigation involving assessment of As2O3 on tumor cell growth in mice indicated that As2O3 also inhibited in vivo tumor growth. As2O3 as an inhibitor of cervical cancer proliferation both in vitro and in vivo suggests a potential clinical application in cervical cancer therapies.