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 As203 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.
Yu
Jing
J
State Key Laboratory of Moleculor Ontology, Cancer Institote, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Qian
Haili
H
Li
Yunfeng
Y
Wang
Yang
Y
Zhang
Xueyan
X
Liang
Xiao
X
Fu
Ming
M
Lin
Chen
C
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology / Q000627:therapeutic use*; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D053453:Caspase 9; D000077237:Arsenic Trioxide