The Inhibitory Effect And Mechanism Of Apple Polyphenols On Prostate Cancer Cells

Prostate cancer is the most commonly diagnosed cancer among men,and it is also the second deadliest malignancy in men.Apple polyphenol(AP)is a natural biologically active substance,some of its monomer components have anti-tumor effects on some cancers,and studies have shown that apple polyphenols can inhibit the proliferation and metastasis of breast cancer cells.But there is almost no research on prostate cancer,so this article mainly studies whether apple polyphenols have an inhibitory effect on prostate cancer.It is hoped that it can provide new ideas for subsequent food-borne substances,especially polyphenols,as potential drugs for anti-prostate cancer.In this study,the CCK8 method was used to detect the proliferation inhibitory effects of apple polyphenols on different prostate cancer cell lines and NIH3T3 cells.The results showed that the IC50 values of apple polyphenols 24 h after the treatment of LNCAP,22RV1 and PC3 cells were 16.52?g/m L,22.21?g/m L,284.5?g/m L,and there was no obvious toxicity to NIH3T3 cells at this concentration;the substance components in apple polyphenols were detected by HPLC,and the results showed that apple polyphenols contain chlorogenic acid(27%),phlorizin(10.06%),Proanthocyanidin B2(4.51 %),EGCG(5.85%),and quercetin(1.43%).The inhibitory effect of different substances on the proliferation of LNCAP cells was detected by the method of CCK8,and the results showed that the inhibitory effect of a single component on LNCAP cells was not obvious.Then,the cell scratch test and transwell test were used to detect cell migration and invasion,and the clone formation test was used to detect cell proliferation.The results showed that apple polyphenols inhibited the migration,invasion and formation of cell clones of these two kinds of cells;flow cytometry was used Detection of cell apoptosis and cell cycle,the results show that apple polyphenols promote cell apoptosis and block cell cycle.The expression of AR and PSA was detected by Western blotting and real-time fluorescent quantitative PCR.The results showed that apple polyphenols down-regulated the expression of AR and PSA;Western blotting was used to detect the effect of apple polyphenols on the stability and nuclear localization of AR,and the effect on the PI3K/AKT/m TOR signaling pathway,The results indicate that apple polyphenols may promote the degradation of AR through the ubiquitin-proteasome pathway,and have no effect on the nuclear localization of AR,but can down-regulate the expression of PI3K/AKT/m TOR related proteins.Finally,animal experiments were conducted to evaluate the effects of apple polyphenols in vivo.The results showed that apple polyphenols inhibited the growth of 22RV1 transplanted tumors and down-regulated the expression of AR and PSA.In summary,the conclusions drawn from this study:? Apple polyphenols inhibit the proliferation of prostate cancer cells,especially AR positive prostate cancer cells have a better inhibitory effect;? The components of apple polyphenols: chlorogenic acid,phlorizin,Proanthocyanidin B2,EGCG,quercetin and other substances;? Apple polyphenols inhibit the migration,invasion and clonal formation of LNCAP and 22RV1 cells,promote cell apoptosis,block cell cycle,and inhibit AR expression and PI3K/AKT/m TOR signal pathways;? Apple polyphenols can inhibit the growth of 22RV1 transplanted tumors.