Ilicicolin C Suppresses the Progression of Prostate Cancer by Inhibiting PI3K/AKT/mTOR Pathway

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2024 May 27

PMID 38801644

Authors

Xia Gan

Xiaowei Luo

Jingqin Chen

Wenxuan Fang

Mingyi Nie

Humu Lu

Yonghong Liu

Xueni Wang

Affiliations

Soon will be listed here.

Abstract

Aberrant activation of the PI3K/AKT pathway is a driving factor in the development of prostate cancer. Therefore, inhibiting the function of the PI3K/AKT signaling pathway is a strategy for the treatment of prostate cancer. Ilicicolin C is an ascochlorin derivative isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501. Which has anti-inflammatory activity, but its activity against prostate cancer has not yet been elucidated. MTT assay, plate clone-formation assay, flow cytometry and real-time cell analysis technology were used to detect the effects of ilicicolin C on cell viability, proliferation, apoptosis and migration of prostate cancer cells. Molecular docking software and surface plasmon resonance technology were used to analyze the interaction between ilicicolin C and PI3K/AKT proteins. Western blot assay was performed to examine the changes in protein expression. Finally, QikProp software was used to simulate the process of ilicicolin C in vivo, and a zebrafish xenograft model was used to further verify the anti-prostate cancer activity of ilicicolin C in vivo. Ilicicolin C showed cytotoxic effects on prostate cancer cells, with the most significant effect on PC-3 cells. Ilicicolin C inhibited proliferation and migration of PC-3 cells. It could also block the cell cycle and induce apoptosis in PC-3 cells. In addition, ilicicolin C could bind to PI3K/AKT proteins. Furthermore, ilicicolin C inhibited the expression of PI3K, AKT and mTOR proteins and could also regulate the expression of downstream proteins in the PI3K/AKT/mTOR signaling pathway. Moreover, the calculations speculated that ilicicolin C was well absorbed orally, and the zebrafish xenograft model confirmed the in vivo anti-prostate cancer effect of ilicicolin C. Ilicicolin C emerges as a promising marine compound capable of inducing apoptosis of prostate cancer cells by counteracting the aberrant activation of PI3K/AKT/mTOR, suggesting that ilicicolin C may be a viable candidate for anti-prostate cancer drug development. These findings highlight the potential of ilicicolin C against prostate cancer and shed light on its mechanism of action.

Citing Articles

Antiproliferative effects of resorcylic acid lactones from the Beibu Gulf coral-derived fungus GXIMD 02512 on prostate cancer cells.

Wang J, Lu H, Fang W, Lin M, Feng Y, Qi X RSC Adv. 2024; 14(52):38697-38705.

PMID: 39654917 PMC: 11626384. DOI: 10.1039/d4ra06292b.

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