Abstract 6351: A novel NSC small molecule inhibitor, inhibits proliferation and invasion of triple-negative breast cancer cells

Abstract

Abstract Treatment of patients with Triple-negative breast cancer (TNBC) has been challenging due to the absence of well-defined molecular targets and high invasive and proliferative capacities of these cells. Current treatments against TNBC have shown minimal activity due to the high recurrence rate in the patients. There is, therefore, a pressing need for novel and efficacious therapies against TNBC. Here, we found a novel small molecule inhibitor with potent anti-tumor activity against TNBC cells. Anti-proliferative effects of NSC small molecule inhibitor were determined using 2D and 3D culture cell proliferation. Propium iodide staining was performed to analyze cell cycle distribution and Annexin/PI assay was carried out to evaluate the induction of apoptosis. Western blot analyses, proteomic and gene array techniques were applied to elucidate the molecular mechanisms underlying the anti-tumor activity of the small molecule inhibitor. Our data show that our NSC small molecule inhibitor, reduced the proliferation of a panel of breast cancer cells, particularly, TNBC cells through the induction of apoptosis but not cell cycle arrest. Proteomic and gene array analysis implicated a myriad of canonical signaling pathways including cell death, and cell survival. Furthermore, we found that treatment with NSC small molecule inhibitor impaired TNBC cell migration and invasion via expression reduction of the epithelial-to-mesenchymal transition (EMT) markers. In addition, we found that NSC small molecule inhibitor decreased TNBC cell proliferation and clonogenic survival and induced apoptotic cell death through inhibition of the anti-apoptotic proteins. Altogether, our data indicate that NSC small molecule inhibitor may exhibit anti-tumor activity in TNBC cells and provide a rationale for further investigation of the potential of NSC small molecule inhibitor as an attractive therapeutic drug for TNBC. We are currently in the process of validating our proteomic data. Further in-depth investigations are required to evaluate the exact targets and mechanism of this potent small molecule inhibitor, and its anti-neoplasm effects on TNBC in vivo. Citation Format: Hassan Yousefi. A novel NSC small molecule inhibitor, inhibits proliferation and invasion of triple-negative breast cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6351.