In:
Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-8-10)
Abstract:
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 Fusarium equiseti 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 50 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 in vivo . Taken together, these findings indicated that 5′-epiequisetin showed an anti–prostate cancer effect by inducing apoptosis and inhibiting cell proliferation and migration both in vitro and in vivo , suggesting a promising lead compound for the pharmacotherapy of prostate cancer.
Type of Medium:
Online Resource
ISSN:
1663-9812
DOI:
10.3389/fphar.2022.920554
DOI:
10.3389/fphar.2022.920554.s001
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2587355-6
SSG:
15,3
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