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4-Hydroxyderricin Promotes Apoptosis and Cell Cycle Arrest through Regulating PI3K/AKT/mTOR Pathway in Hepatocellular

Xiang Gao1, Yuhuan Jiang1, Qi Xu1

  • 1Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao 266071, China.

Foods (Basel, Switzerland)
|September 28, 2021
PubMed

Insights

4-hydroxyderricin (4-HD), a natural compound from Angelica keiskei, inhibits liver cancer cells by inducing apoptosis and cell cycle arrest. It suppresses the PI3K/AKT/mTOR pathway, offering a potential therapeutic strategy for hepatocellular carcinoma (HCC).

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Hepatocellular carcinoma (HCC) is a major global health concern with limited effective treatments.
  • Natural compounds are being explored for their anti-cancer properties.
  • The inhibitory mechanisms of 4-hydroxyderricin (4-HD) from Angelica keiskei on liver cancer remain largely unelucidated.

Purpose of the Study:

  • To investigate the inhibitory effects of 4-hydroxyderricin (4-HD) on hepatocellular carcinoma (HCC) cells.
  • To clarify the mechanisms underlying 4-HD's anti-cancer activity, focusing on apoptosis and cell cycle regulation.
  • To explore the role of the PI3K/AKT/mTOR signaling pathway in 4-HD-mediated effects.

Main Methods:

  • Cell viability and activity assays were performed on HepG2 and Huh7 HCC cell lines.
  • Western blot analysis was used to assess protein expression levels of apoptosis-related and cell cycle-related genes.
  • The expression of key proteins in the PI3K/AKT/mTOR pathway (PI3K, p-PI3K, p-AKT, p-mTOR) was quantified.
  • The effect of a PI3K inhibitor (LY294002) in combination with 4-HD was evaluated.

Main Results:

  • 4-hydroxyderricin (4-HD) significantly reduced the survival rate and activity of HepG2 and Huh7 cells.
  • 4-HD treatment led to increased expression of apoptosis-related proteins and decreased expression of cell cycle-related proteins.
  • 4-HD down-regulated the protein expression of PI3K, p-PI3K, p-AKT, and p-mTOR.
  • Co-administration of 4-HD with a PI3K inhibitor (LY294002) potentiated apoptosis and cell cycle arrest in HCC cells.

Conclusions:

  • 4-hydroxyderricin (4-HD) exhibits significant inhibitory effects on hepatocellular carcinoma (HCC) cell proliferation.
  • 4-HD suppresses HCC progression by inducing apoptosis and cell cycle arrest.
  • The anti-cancer effects of 4-HD are mediated through the modulation of the PI3K/AKT/mTOR signaling pathway.
Keywords:
Angelica keiskeianti-tumorapoptosiscell cyclechalconemechanism

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