Chlorogenic Acid Decreases Malignant Characteristics of Hepatocellular Carcinoma Cells by Inhibiting DNMT1 Expression.

DNMT1 chlorogenic acid hepatocellular carcinoma migration proliferation

Journal

Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923

Informations de publication

Date de publication:
2020
Historique:
received: 09 12 2019
accepted: 26 05 2020
entrez: 14 7 2020
pubmed: 14 7 2020
medline: 14 7 2020
Statut: epublish

Résumé

Hepatocellular carcinoma (HCC) is the most common malignant tumor of the adult liver, exhibiting rapid progression and poor prognosis. Chlorogenic acid (CGA), a polyphenol, has several biological activities, including the suppression of liver cancer cell invasion and metastasis. Increased levels or alterations in the function of DNMT1 are associated with the inactivation of tumor suppressor genes. However, the CGA-affected DNMT1 expression mediated mechanism is still unclear. The human hepatocellular carcinoma (HCC) HepG2 cells were treated with a positive control drug (5-AZA) or varying doses of CGA. DNA methyltransferase 1 (DNMT1) protein levels and other relevant proteins were evaluated using Western blotting and immunocytochemistry. Cell-cycle analysis was performed by flow cytometry-based PI staining, and cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The transwell invasion and wound healing assays were used to evaluate cell migration and invasion. In vivo proliferation of the HCC cells was detected. We investigated the expression of DNMT1, p53, p21, p-ERK, MMP-2, and MMP-9 in tumors using immunohistochemical analysis. Our results showed that CGA inhibited the proliferation, colony formation, invasion, and metastasis of HepG2 cells both CGA can suppress liver cancer cell proliferation, invasion, and metastasis through several pathways. CGA could serve as a candidate chemopreventive agent for HCC.

Sections du résumé

BACKGROUND BACKGROUND
Hepatocellular carcinoma (HCC) is the most common malignant tumor of the adult liver, exhibiting rapid progression and poor prognosis. Chlorogenic acid (CGA), a polyphenol, has several biological activities, including the suppression of liver cancer cell invasion and metastasis. Increased levels or alterations in the function of DNMT1 are associated with the inactivation of tumor suppressor genes. However, the CGA-affected DNMT1 expression mediated mechanism is still unclear.
METHODS METHODS
The human hepatocellular carcinoma (HCC) HepG2 cells were treated with a positive control drug (5-AZA) or varying doses of CGA. DNA methyltransferase 1 (DNMT1) protein levels and other relevant proteins were evaluated using Western blotting and immunocytochemistry. Cell-cycle analysis was performed by flow cytometry-based PI staining, and cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The transwell invasion and wound healing assays were used to evaluate cell migration and invasion. In vivo proliferation of the HCC cells was detected. We investigated the expression of DNMT1, p53, p21, p-ERK, MMP-2, and MMP-9 in tumors using immunohistochemical analysis.
RESULTS RESULTS
Our results showed that CGA inhibited the proliferation, colony formation, invasion, and metastasis of HepG2 cells both
CONCLUSIONS CONCLUSIONS
CGA can suppress liver cancer cell proliferation, invasion, and metastasis through several pathways. CGA could serve as a candidate chemopreventive agent for HCC.

Identifiants

pubmed: 32655395
doi: 10.3389/fphar.2020.00867
pmc: PMC7325898
doi:

Types de publication

Journal Article

Langues

eng

Pagination

867

Informations de copyright

Copyright © 2020 Liu, Feng, Li, Hu, Zhang, Huang, Shi, Ran, Hou, Zhou and Wang.

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Auteurs

Yao Liu (Y)

Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Ying Feng (Y)

Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Yuxin Li (Y)

Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Ying Hu (Y)

Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Qun Zhang (Q)

Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Yunyi Huang (Y)

Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Ke Shi (K)

Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Chongping Ran (C)

Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Jie Hou (J)

Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Guiqin Zhou (G)

Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Xianbo Wang (X)

Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Classifications MeSH