Abstract 4465: Inhibition of tumor growth, lymphangiogenesis, and metastasis by iron chelators, deferoxamine and deferasirox, in breast cancers

Abstract

Abstract Iron participates in a range of reactions that are necessary for cell viability and cell proliferation and it has been reported that iron depletion by chelator inhibits the proliferation of various cancer cells. Among the different kind of iron chelators, deferoxamine is the most widely studied molecule as an anti-tumor agent. Deferasirox is a new rationally-designed oral iron chelator and there are few reports regarding in vitro and in vivo effect on myeloid leukemia cells.This study was undertaken to evaluate the in vitro and in vivo effects of DFX (deferoxamine) and DFS (Deferasirox) on anti-cancer activities in breast cancer cells and to define molecular mechanisms underlying these effects. We found that DFX or DFS displayed significant anti-proliferative activity in a dose-and time-dependent manner in MDA-MB-231 and MDA-MB-435 cells. DFX or DFS treatment led to the enhanced percentages of apoptotic cell, which was mediated through the mitochondrial death pathway that requires up-regulation of Bad phosphorylation, PUMA, and caspase-3 /-9 activities. In addition, DFX or DFS treatment significantly attenuated the motility and invasiveness of metastatic breast cancer cells, which is attributed to the decrease in EMT process and lymphangiogenesis. Importantly, the in vivo study revealed that DFX or DFS retarded tumor growth and suppressed the metastatic capacity to lymph nodes by down-regulating lymphangiogenesis in the orthotropic breast tumor model. These data demonstrate that DFX or DFS induces anti-cancer activity of breast cancer cells by both inducing apoptosis and suppressing metastasis in vitro and in vivo. Hence, DFX and DFS could provide another strategy for treating breast cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4465. doi:10.1158/1538-7445.AM2011-4465