The Natural Compound Myricetin Effectively Represses the Malignant Progression of Prostate Cancer by Inhibiting PIM1 and Disrupting the PIM1/CXCR4 Interaction

Abstract

Background/Aims: Natural compounds are a promising resource for anti-tumor drugs. Myricetin, an abundant flavonoid found in the bark and leaves of bayberry, shows multiple promising anti-tumor functions in various cancers. Methods: The cytotoxic, pro-apoptotic, and anti-metastatic effects of myricetin on prostate cancer cells were investigated in both in vitro and in vivo studies. Short-hairpin RNA knockdown of the proviral integration site for Moloney murine leukemia virus-1 (PIM1), pull-down and co-immunoprecipitation assays, and an intracellular Ca2+ flux assay were used to investigate the potential underlying mechanism of myricetin. ONCOMINE database data mining and immunohistochemical analysis of prostate cancer tissues were used to evaluate the expression of PIM1 and CXCR4, as well as the correlation between PIM1 and CXCR4 expression and the clinicopathologic characteristics and prognoses of prostate cancer patients. Results: Myricetin exerted selective cytotoxic, pro-apoptotic, and anti-metastatic effects on prostate cancer cells by inhibiting PIM1 and disrupting the PIM1/CXCR4 interaction. Moreover, PIM1 and CXCR4 were coexpressed and associated with aggressive clinicopathologic traits and poor prognosis in prostate cancer patients. Conclusion: These results offer preclinical evidence for myricetin as a potential chemopreventive and therapeutic agent for precision medicine tailored to prostate cancer patients characterized by concomitant elevated expression of PIM1 and CXCR4.

Keywords

• Prostate cancer
• Myricetin
• PIM1
• CXCL12-CXCR4 axis
• Small molecular inhibitor