Curcumin Induces Apoptosis by Suppressing XRCC4 Expression in Hepatocellular Carcinoma

AbstractCurcumin is a chemical with various pharmacological activities used for cancer treatment. It inhibits hepatocellular carcinoma (HCC) by inducing apoptosis. Here, the mechanism underlying the effect of curcumin on the apoptosis of HCC cells was studied. Cell counting kit-8 and plate cloning assays were used to assess the proliferation of HCC cells, and acridine orange/ethidium bromide and Annexin V/PI staining were used to analyze their apoptosis. HCC xenograft tumor models were established to validate anti-cancer effects of curcumin. Expression levels of XRCC4 protein in tumor tissues were assessed by immunohistochemistry. Correlation between XRCC4 expression and the prognosis of patients with HCC was analyzed by integrating publicly available gene expression data. Curcumin inhibited HCC cells proliferation in a dose-dependent manner. Compared with the control group, curcumin significantly promoted the apoptosis of HCC cells in vitro and in vivo. Immunohistochemical analysis revealed that curcumin downregulated XRCC4 expression levels in HCC tissues. Prognosis of HCC patients with high XRCC4 expression was poorer than that of patients with low XRCC4 expression. Therefore, curcumin exerts anti-cancer effects by inhibiting cell proliferation and promoting cell apoptosis in HCC. This may be due to curcumin interference in the repair process of the nonhomologous DNA terminal link of HCC cells by downregulating XRCC4 expression. Author ContributionsSW, JL, and DW were responsible for the conception and design of the study. SW, WW, YL, and EX performed the in vivo experiments. JL and JJ conducted the in vitro experiments. LL collected and analyzed the data. SW and LL wrote the original manuscript. DW and JL reviewed and edited the final manuscript. All authors contributed valuable input and feedback to previous versions of the manuscript. All authors read and approved the published version of the manuscript.Disclosure StatementNo potential conflict of interest was reported by the authors.Ethics Approval and Consent to ParticipateThis study does not contain any studies with human participants performed by any of the authors.Data Availability StatementThe data that support the findings of this study are available from the corresponding author upon reasonable request.Additional informationFundingThe work was supported by the Innovation and Entrepreneurship Training Program for College Students under Grant [number X202110440023]; Provincial Medicine and Health Science Technology Development Program Shandong under Grant [number 2017WS822].