Abstract 286: Cucurbitacin B inhibits epithelial-to-mesenchymal transition in breast cancer cells through Snail downregulation.

Abstract

Abstract Metastasis is a primary cause of about 90% of cancer related deaths worldwide. It is associated with epithelial to mesenchymal characteristics transition (EMT), which helps in attaining migratory phenotype by tumor cells. Cucurbitacin B (CuB), a triterpenoid steroidal compound has been shown to suppress JAK/STAT3 signaling and cause G2/M arrest in cancer cells. However, the role of CuB as an anti-metastatic agent still remains to be elucidated. In the present study, we investigated the effects of CuB on EMT in breast cancer cells. These cells are known to exhibit significant mesenchymal properties that endow aggressive nature. Our results show that CuB significantly suppressed cell migration of MDA-MB-231 cells in wound healing assay. In addition, we also observed reduced cell invasion with CuB treatment using transwell invasion assay. To elucidate the mechanism of these effects, western blotting was performed using whole cell lysates from CuB treated MDA-MB-231 cells. We observed significantly reduced expression of snail and twist with CuB treatment. Snail and twist are known to be repressors of E-cadherin. Generally upregulation of snail and twist mark the initiation of EMT, and eventually leads to loss of epithelial signature of cells. Furthermore, with CuB treatment upregulation of E-cadherin was observed. Transforming growth factor β is known to induce EMT in malignant breast cancer cells. We further investigated the role of CuB on TGFβ induced EMT. Interestingly, we observed that TGFβ induced snail expression was reversed by CuB in MDA-MB-231 cells. Moreover, CuB treatment also contributed protection to the loss of E-cadherin caused by TGFβ treatment. Taken together our results indicate reversal of EMT by CuB treatment in breast cancer cells, which lead to suppression of metastasic ability. However, further in vitro and in vivo mechanistic studies are under progress. [Supported in part by R01 grant CA129038 (to S.K.S) awarded by the National Cancer Institute]. Citation Format: Parul Gupta, Sanjay K. Srivastava. Cucurbitacin B inhibits epithelial-to-mesenchymal transition in breast cancer cells through Snail downregulation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 286. doi:10.1158/1538-7445.AM2013-286