4-Methoxydalbergione Elicits Anticancer Effects by Upregulation of GADD45G in Human Liver Cancer Cells

J Healthc Eng. 2023 Feb 1:2023:6710880. doi: 10.1155/2023/6710880. eCollection 2023.

Abstract

Background: 4-Methoxydalbergione (4MOD) is a flavonoid isolated from the heartwood of Dalbergia. Studies have demonstrated that 4MOD exerts anticancer activities on bladder cancer and astrocytoma. However, the anticancer activity of 4MOD in hepatocellular carcinoma (HCC) remains unknown. This study aims to examine its anticancer activities and mechanisms in human liver cancer cells.

Methods: CCK-8, colony forming, wound healing, transwell migration, and AnnexinV/PI assays were used to assess the anticancer effects of 4MOD in HCC cells. RNA sequencing (RNA-Seq) was selected to explore the possible mechanisms underlying the anti-HCC activity of 4MOD. The mRNA expression levels of target genes were verified through quantitative real-time PCR (qRT-PCR). A lentiviral shRNA interference technique was used to silence GADD45G expression. GADD45G knockdown was employed to confirm the crucial role of GADD45G in the 4MOD-mediatedanti-HCC effects.

Results: 4MOD inhibited HCC cells' proliferation and migration and promoted tumor cell apoptosis. RNA-Seq and qRT-PCR analyses revealed that 4MOD treatment increased GADD45G expression. Silencing GADD45G reversed 4MOD-mediated inhibition of proliferation, migration, and promotion of apoptosis.

Conclusions: Our findings show that 4MOD elicits anti-HCC effects by upregulating GADD45G expression and could be a valuable anticancer agent for liver cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / genetics
  • Cell Line, Tumor
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / genetics
  • Up-Regulation

Substances

  • 4-methoxydalbergione
  • GADD45G protein, human
  • Intracellular Signaling Peptides and Proteins