Effects of brucine on mitochondrial apoptosis and expression of HSP70 in prostate cancer cells

Abstract

Background: Most prostate cancer patients are already in the middle/advanced stages of the disease at the time of detection. Whether brucine can regulate apoptosis in prostate cancer cells through the expression of heat shock protein 70 (HSP70) has not been reported. We preliminarily investigated the effects of brucine on the mitochondrial apoptosis and HSP70 expression of prostate cancer cells and analyzed brucine's possible mechanisms in the hope of providing an experimental basis for its clinical application. Methods:The effect of brucine on the activity of PC-3 cells was determined by the methodology of tetrazolium (MTT) assay method. The effect of brucine on apoptosis was measured by Hoechst 33258 staining and flow cytometry, and western blotting was used to detect the expression levels of the apoptosisrelated heat shock protein 70 (HSP70), anti-apoptotic protease activating factor 1 (Apaf-1) and anti-cysteine protease-3 (caspase-3).Results: At 24 and 48 h, the activity of human prostate cancer PC-3 cells in the low, medium, and high dose brucine groups was significantly lower than that of the control group, with a dose-dependent difference (P<0.01). The nuclei of the control group fluoresced uniformly with intact nuclei, whereas the nuclei of the brucine group appeared crinkled, and dense granular masses of strong blue fluorescence were visible. The apoptosis rate of human prostate cancer PC-3 cells in the low, medium, and high dose brucine groups was significantly higher than that in the control group (P<0.01) and was dose-dependent. The expression levels of the HSP70 protein in the human prostate cancer PC-3 cells in the low, medium, and high dose brucine groups were significantly lower than those in the control group, while the expression levels of the Apaf-1 and caspase-3 proteins were significantly higher than those in the control group (P<0.01) and showed a dosedependent relationship.Conclusions: Brucine downregulated HSP70 expression in human prostate cancer PC-3 cells and inhibited the mitochondrial apoptotic signaling pathway, thus acting as an anti-apoptotic agent.

Induction of ferroptosis by brucine suppresses gastric cancer progression through the p53-mediated SLCA711/ALOX12 axis

“…The brucine-mediated inhibition of other tumors has been extensively studied. For example, brucine induces prostate cancer cells to undergo apoptosis via heat shock protein 70 (HSP70) [ 28 ]. In cervical cancer, brucine induces apoptosis, attenuates inflammation, and slows the growth of cells by inhibiting PI3K/AKT/mTOR signaling [ 13 ].…”

Chinese herbal medicines for prostate cancer therapy: From experimental research to clinical practice

“…In the low, medium and high dose brucine groups, the expression levels of HSP70 protein were significantly lower than those in the control group. Brucine inhibited the expression of HSP70 and promoted the apoptosis of PC-3 cells ( Yan et al, 2022 ). Artemisinin inhibited c-Jun, p-c-Jun, NF-κB, p-Akt, caused PC-3 cell death via caspase-dependent intrinsic signaling cascade ( Ahmad et al, 2020 ).…”