Abstract 2103: XB05: a promising small molecule for cancer therapy.

Abstract

XB05 is synthetic small molecule which was serendipitously discovered to have potent anticancer properties. XB05 displays selectivity for malignant cells over non-malignant cells. Human myeloid leukemia cells (U937) and human lung cancer cells (A549) treated with XB05 show an increase in oxidative stress, DNA damage and a mixed apoptotic and necrotic mechanism of cell death. We conducted a COMPARE analysis to search for correlations between XB05 response and gene expression using publicly available microarray studies of the National Cancer Institute 60 cell line panel. This analysis uncovered a correlation between cell death in response to XB05 and expression of the transcription factor, SOX9. We find that SOX9 is differentially expressed across a panel of human lung cancer cell lines. MTT proliferation and clonogenic cell survival assays suggest that SOX9 expression positively correlates with the sensitivity of lung cancer cells to XB05. Furthermore, we show that siRNA knockdown of SOX9 recapitulates the phenotype of XB05-induced cell death, and that SOX9 may be downregulated at the protein level by XB05 treatment. Overall, these data demonstrate potent activity of XB05 against human cancer cells via a novel mechanism of action, and a potential role for SOX9 as a biomarker for selection and monitoring of therapy with XB05. Citation Format: Francesca R. Salipur, Elsa M. Reyes Reyes, Bo Xu, Ned Smith, Jian Cai, Gerald B. Hammond, Paula J. Bates. XB05: a promising small molecule for cancer therapy. [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 2103. doi:10.1158/1538-7445.AM2013-2103