PMID- 35860003 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231221 IS - 1741-427X (Print) IS - 1741-4288 (Electronic) IS - 1741-427X (Linking) VI - 2022 DP - 2022 TI - Cantharidin Inhibits Proliferation of Liver Cancer by Inducing DNA Damage via KDM4A-Dependent Histone H3K36 Demethylation. PG - 2197071 LID - 10.1155/2022/2197071 [doi] LID - 2197071 AB - OBJECTIVE: To investigate the effect of cantharidin on DNA damage in hepatocellular carcinoma cells and its possible mechanism. METHODS: Cell proliferation assay and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were used to analyze the effects of cantharidin on cell proliferation and apoptosis of hepatocellular carcinoma cells. The expression levels of DNA damage markers H2AX and P21 were analyzed by qRT-PCR. The expression of KDM4A and H3K36me3 was observed by western blot. The expression of KDM4A was regulated by siRNA or plasmid transfection. The effect of KDM4A on DNA damage induced by cantharidin in liver cancer was observed after overexpression and addiction of KDM4A. RESULTS: Cantharidin can significantly inhibit the growth of hepatocellular carcinoma cells and induce apoptosis of hepatocellular carcinoma cells. Cantharidin enhances the chemotherapy sensitivity of liver cancer by targeting the upregulation of KDM4A and the regulation of DNA damage induced by H3K36me3. Overexpression of KDM4A enhances DNA damage induced by cantharidin in HCC. KDM4A silencing attenuated the damage of cantharidin to the DNA of HCC cells. CONCLUSION: Cantharidin can inhibit the growth and promote apoptosis of hepatocellular carcinoma cells. Meanwhile, cantharidin can induce DNA damage in HCC cells. Mechanism studies have shown that cantharidin induces DNA damage through the demethylation of KDM4A-dependent histone H3K36. CI - Copyright (c) 2022 Chao Wei et al. FAU - Wei, Chao AU - Wei C AD - Infectious Disease Department, Qijiang Hospital of the First Affiliated Hospital of Chongqing Medical University, Chongqing 401420, China. FAU - Deng, Xiangui AU - Deng X AD - Infectious Disease Department, Wenlong Hospital of Qijiang, Chongqing 401420, China. FAU - Gao, Shudi AU - Gao S AD - Infectious Disease Department, Taiyuan Hospital of Traditional Chinese Medicine, Taiyuan 030009, Shanxi Province, China. FAU - Wan, Xuemei AU - Wan X AD - Infectious Disease Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610032, Sichuan Province, China. FAU - Chen, Jing AU - Chen J AUID- ORCID: 0000-0002-9757-6027 AD - Infectious Disease Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610032, Sichuan Province, China. LA - eng PT - Journal Article PT - Retracted Publication DEP - 20220711 PL - United States TA - Evid Based Complement Alternat Med JT - Evidence-based complementary and alternative medicine : eCAM JID - 101215021 RIN - Evid Based Complement Alternat Med. 2023 Dec 13;2023:9785474. PMID: 38125128 PMC - PMC9293552 COIS- The authors declare that they have no conflicts of interest. EDAT- 2022/07/22 06:00 MHDA- 2022/07/22 06:01 PMCR- 2022/07/11 CRDT- 2022/07/21 02:23 PHST- 2022/03/16 00:00 [received] PHST- 2022/05/19 00:00 [revised] PHST- 2022/05/27 00:00 [accepted] PHST- 2022/07/21 02:23 [entrez] PHST- 2022/07/22 06:00 [pubmed] PHST- 2022/07/22 06:01 [medline] PHST- 2022/07/11 00:00 [pmc-release] AID - 10.1155/2022/2197071 [doi] PST - epublish SO - Evid Based Complement Alternat Med. 2022 Jul 11;2022:2197071. doi: 10.1155/2022/2197071. eCollection 2022.