Abstract 703: An anthelmintic drug, flubendazole, exerts antitumor effects in triple-negative breast cancer via targeting cancer stem-like properties

Triple-negative breast cancer (TNBC) remains challenging due to the absence of established molecular targets for the phenotype. These tumors tend to be more aggressive with a higher risk of recurrence and metastasis, leading to poorer clinical outcomes. Flubendazole (FLU) is a widely used anthelmintic agent that also exhibits anticancer activity in several cancer types. The objective of the present study was to investigate the effects of FLU on cell proliferation, apoptosis and breast cancer stem cell (BCSC)-like properties in TNBC. The effect of FLU on TNBC cell lines in vitro was evaluated in terms of apoptosis, cell cycle distribution, caspase-3/-7 activity and BCSC-like characteristics. An orthotopic allograft model with 4T1 mammospheres was used to examine the effect of FLU on tumor growth and angiogenesis in vivo. FLU efficiently induced apoptosis with accompanied by activation of caspase-3 and -7, and PARP cleavage in TNBC. FLU-induced apoptosis is associated with the accumulation of G2/M phase cells by tubulin degradation, leading to mitotic catastrophe. Interestingly, FLU significantly suppressed BCSC-like properties in TNBC, as evidenced by a marked inhibition of ALDH1 activity, the CD44high/CD24low and CD49fhigh/CD24high subpopulations, and the subsequent impairment of mammosphere formation in vitro. This appears to contribute toward the suppression of BCSC-enriched tumor burden and intra-tumoral angiogenesis in TNBC allografts, together with a significant downregulation of ALDH1A1 and CD49f expression in vivo. Our findings suggest that FLU kills not only rapid proliferating tumor cells but also effectively eradicates BCSC-like cells in vitro and in vivo. These findings warrant further investigation of flubendazole as a potential treatment for triple-negative breast cancer. Citation Format: Yoon-Jae Kim, Eunhye Oh, Tae-Min Cho, Seojin Jang, Jung Min Park, Soeun Park, Minsu Park, Ji Young Kim, Jae Hong Seo. An anthelmintic drug, flubendazole, exerts antitumor effects in triple-negative breast cancer via targeting cancer stem-like properties [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 703.