Abstract 2513: Arsenic trioxide induces depolymerization of microtubules in an acute promyelocytic leukemia cell line

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Arsenic trioxide (ATO) treatment has been used in recent decades to achieve clinical remission in patients with acute promyelocytic leukemia (APL). The biological basis for ATO treatment has been explained as being mediated through anti-proliferation, anti-angiogenesis, and apoptosis in both APL and solid tumor cells. Arsenic trioxide has been shown to affect microtubules such that dysfunction of the cellular cytoskeleton is induced, which ultimately leads to cell death. In this study, we reported that ATO disrupts tubulin assembly and results in microtubule dysfunction, inducing cell death in an APL cell line. ATO markedly enhanced the depolymerization of microtubules. Analysis of posttranslational modifications of microtubules also revealed that ATO decreased modified forms of the polymerized tubulin portion in adose-dependent manner. Immunocytochemical investigation showed that ATO changed the cellular microtubule network and inhibited the formation of polymerized microtubules. These alterations in microtubules suggest that ATO increases the depolymerized form of tubulin in the cells, potentially through its effect on the attenuation of spindle dynamics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2513.