Abstract 2: Flavokawain A targets cancer stem cells for inhibiting the growth of prostate cancer

Abstract Prostate cancer stem cells (PCSC) are small tumor subpopulations capable of self-renewal and driving prostate cancer heterogeneity, which is critical for cancer initiation, recurrence, and development of therapeutic resistance. Thus, there’s an urgent need to explore and develop new CSC targeting agents. Flavokawain A (FKA), a novel chalcone from kava plant, can selectively inhibit the growth of pRb deficient cell lines and result in a proteasome-dependent and ubiquitination-mediated Skp2 (S-phase kinase-associated protein 2) degradation, while the potential of FKA to target PCSC is unknown. Therefore, we evaluated the effects of FKA on PCSC self-renewal both in vitro and in vivo. FKA treatment decreased both size and numbers of the tumor spheroids growing from CD44+/CD133+ tumor stem cells, which were sorted out from the prostate tumor cell line DU145 and 22RV1. Expression of the stem cell markers Nanog, Oct4, and Sox2 were all downregulated in the cancer spheroids treated with FKA. Growth of the 22RV1CD44+/CD133+ xenograft tumors was significantly inhibited in FKA diet-fed mice compared to the vehicle control diet-fed mice. Immunohistochemistry analysis revealed less positive Ki67, Nanog, and Oct4 cells in tumor tissues from the FKA dietary group than those from the control dietary group. These results demonstrated that FKA can inhibit prostate cancer stemness and suggested a potential role of FKA for preventing prostate cancer recurrence by targeting PCSC. Citation Format: Liankun Song, Merci Mino, Jana Yamak, Vyvyan Nguyen, Derron Lopez, Victor Pham, Ali Fazelpour, Vinh Le, Dongjun Fu, Matthew Tippin, Xiaolin Zi. Flavokawain A targets cancer stem cells for inhibiting the growth of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2.