Abstract 4123: Thymoquinone inhibits bone metastasis in a breast cancer mouse model by modulating CXCR4/CXCL12 signaling axis

Abstract

Abstract Several lines of evidence(s) indicate that CXCR4 overexpression has been correlated with distant site metastasis and poor overall survival rate in patient with breast cancer. The tumor metastasis promoting molecule CXCR4 is considered as a potential therapeutic target for inhibiting breast cancer metastasis. Thus, novel agents that can down-regulate CXCR4 expression have potential against breast cancer metastasis. In the present report we investigated the effect of thymoquinone (TQ), derived from the seeds of medicinal plant Nigella sativa, on the expression and regulation of CXCR4 in breast cancer cells. In addition, we evaluated the effect of TQ in a metastasis mouse model established by intracardiac injection of luciferase tagged MDA-MB-231 breast cancer cells that metastasize to the bones. We observed that TQ could inhibit the expression of CXCR4 in MCF-7 and MDA-MB-231 cells in a dose and time dependent manner. TQ (2 mg/kg or 4 mg/kg) treatment for four weeks significantly inhibited tumor growth and significantly reduced metastasis to multiple vital organs, including lungs, brain and bone. Immuno-histochemical analysis of the lung and brain tissue showed significant reduction in CXCR4, Ki67, MMP9, VEGFR2 and COX2 expression compared to control tissues. TQ treatment also reduced the overall bone tumor burden. Overall, our results show that TQ exerts its antitumor and anti-metastatic effects by downregulation of CXCR4 expression both in vitro and in vivo thus may have possible potential for the treatment of breast cancer. Acknowledgement: This work was supported by NUHS Basic Seed Research grant to Prof. Benny Tan. Citation Format: Muthu K. Shanmugam, Annie Hsu, Kam Man Hui, Benny K.H. Tan, Gautam Sethi. Thymoquinone inhibits bone metastasis in a breast cancer mouse model by modulating CXCR4/CXCL12 signaling axis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4123.