Analysis of regulating activities of 5'-epiequisetin on proliferation, apoptosis, and migration of prostate cancer cells and .

Advanced prostate cancer has a poor prognosis, and it is urgent to develop new effective drugs. 5'-Epiequisetin is a tetramic acid derivative which was isolated from a marine sponge-derived fungus in our previous study. In this study, 5'-epiequisetin showed cytotoxicity against four prostate cancer cell lines, namely, LNCaP, 22Rv1, DU145, and PC-3 cells, with the lowest IC value of 4.43 ± 0.24 μM in PC-3 cells. Further studies showed that it could dramatically regulate the clonal colony formation, apoptosis, and migration of PC-3 cells. In addition, flow cytometry data showed that 5'-epiequisetin could block the cell cycle at the G1 phase. Proteome profiler array and Western blot revealed that 5'-epiequisetin could regulate the expression of proteins responsible for cell proliferation, apoptosis, and migration. 5'-Epiequisetin regulated the expression of PI3K, Akt, phosphorylated Akt, and proteins which control the cell cycle. Meanwhile, 5'-epiequisetin upregulated expression of DR5 and cleave-caspase 3, which play important roles in the process of apoptosis. Moreover, when DR5 was silenced by small interfering RNA, the proportion of apoptotic cells induced by 5'-epiequisetin remarkably declined. In addition, 5'-epiequisetin downregulated the expression of survivin which plays a key role in the process of survival and apoptosis. 5'-Epiequisetin also impacted beta-catenin and cadherins, which were associated with cell migration. In addition, 5'-Epiequisetin significantly inhibited the progression of prostate cancer in mice, accompanied by regulating the protein expression of DR5, caspase 8, survivin, and cadherins . Taken together, these findings indicated that 5'-epiequisetin showed an anti-prostate cancer effect by inducing apoptosis and inhibiting cell proliferation and migration both and , suggesting a promising lead compound for the pharmacotherapy of prostate cancer.