Resveratrol inhibits the malignant progression of hepatocellular carcinoma via MARCH1-induced regulation of PTEN/AKT signaling.

Abstract

Resveratrol is a common, naturally occurring polyphenol confirmed with inhibited the cellular effects of carcinogenesis. However, the molecular mechanism underlying resveratrol's action against hepatocellular carcinoma (HCC) is still unclear. In addition, MARCH1 promotes the initiation and progression of HCC, but it is unclear whether resveratrol exerts antitumor efforts by regulating MARCH1 expression. This study determined the molecular mechanisms underlying the antitumor effects of resveratrol in HCC. Resveratrol induced apoptosis and inhibited the proliferation, migration, and invasion of HCC cell lines (HepG2 and Hep3B). In addition, it inhibited MARCH1 and phospho-protein kinase B (p-AKT) expression but upregulated the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) dose-dependently both in vitro and in vivo. MARCH1 knockdown by small interfering RNA (siRNA) also increased PTEN expression. Meanwhile, MK2206 (an AKT inhibitor) and bisperoxovanadium (BPV; a PTEN inhibitor) combined with resveratrol decreased MARCH1 expression more than the single-treatment HCC group. These results suggested that resveratrol affects the biological characteristics of HCC via downregulation of MARCH1 expression.

• Authors: Hanhan Dai, Minjing Li, Wei Yang, Xiucui Sun, Peiyuan Wang, Xia Wang, Jiaqi Su, Xu Wang, Xuemei Hu, Mingdong Zhao
• Journal: Aging (Aging (Albany NY)) Vol. 12 Issue 12 Pg. 11717-11731 (06 12 2020) ISSN: 1945-4589 [Electronic] United States
• PMID: 32530437 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• MARCHF1 protein, human
• Ubiquitin-Protein Ligases
• AKT1 protein, human
• Proto-Oncogene Proteins c-akt
• PTEN Phosphohydrolase
• PTEN protein, human
• Resveratrol

Topics

• Animals
• Apoptosis (drug effects)
• Carcinogenesis (drug effects, genetics)
• Carcinoma, Hepatocellular (drug therapy, genetics, pathology)
• Cell Movement (drug effects, genetics)
• Cell Proliferation (drug effects, genetics)
• Disease Progression
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Knockdown Techniques
• Hep G2 Cells
• Humans
• Liver Neoplasms (drug therapy, genetics)
• Mice
• PTEN Phosphohydrolase (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Small Interfering (metabolism)
• Resveratrol (pharmacology, therapeutic use)
• Signal Transduction (drug effects, genetics)
• Ubiquitin-Protein Ligases (genetics, metabolism)
• Xenograft Model Antitumor Assays