Isorhamnetin Inhibited the Proliferation and Metastasis of Androgen-independent Prostate Cancer Cells by Targeting the Mitochondrion-dependent Intrinsic Apoptotic and PI3K/Akt/mTOR Pathway

Overview

Journal Biosci Rep

Specialty Cell Biology

Date 2020 Feb 11

PMID 32039440

Citations 24

Authors

Fangzhen Cai

Yanmei Zhang

Jianwei Li

Sihuai Huang

Ruilin Gao

Affiliations

Soon will be listed here.

Abstract

The present study investigated the effects of Isorhamnetin on two types of prostate cancer cells (androgen-independent and androgen-dependent) and explored its possible mechanisms underlying such effects. Treatment with Isorhamnetin significantly inhibited cell growth and induced lactate dehydrogenase (LDH) release of androgen-independent DU145 and PC3 prostate cancer cells, but exhibited almost no toxicity effect on androgen-dependent LNCaP prostate cancer cell line or normal human prostate epithelial PrEC cells, which was achieved by the induction of apoptosis in a mitochondrion-dependent intrinsic apoptotic pathway. Furthermore, Isorhamnetin inhibited cell migration and invasion in concentration-dependent manners by enhancing mesenchymal-epithelial transition (MET) and inhibiting matrix metalloproteinase (MMP) 2 (MMP-2) and MMP-9 overexpression. In addition, Isorhamnetin also down-regulated the expression of phosphorylated PI3K (p-P13K), Akt (p-Akt), and mTOR (p-mTOR) proteins in both cancer cells, revealing Isorhamnetin to be a selective PI3K-Akt-mTOR pathway inhibitor. In summary, these findings propose that Isorhamnetin might be a novel therapeutic candidate for the treatment of androgen-independent prostate cancer.

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