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. 2022 Mar;11(3):500-507.
doi: 10.21037/tcr-22-209.

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

Affiliations

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

Wei Yan et al. Transl Cancer Res. 2022 Mar.

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 apoptosis-related 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 dose-dependent 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.

Keywords: Brucine; heat shock protein 70; mitochondrial apoptosis; prostate cancer.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-209/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Hoechst staining results of PC-3 cells after brucine treatment. (A) Control group; (B) brucine low dose group; (C) brucine medium dose group; (D) brucine high dose group. Arrows indicate apoptotic cells with a ×40 magnification.
Figure 2
Figure 2
The apoptosis rate of PC-3 cells in each group by flow cytometry. (A) Control group; (B) brucine low dose group; (C) brucine medium dose group; (D) brucine high dose group.
Figure 3
Figure 3
Comparison of HSP70, Apaf-1, and caspase-3 protein expression levels in PC-3 cells in each group. HSP70, heat shock protein 70; Apaf-1, anti-apoptotic protease activating factor 1; caspase-3, anti-cysteine protease-3.

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