Reactive oxygen species-mediated kinase activation by dihydrotanshinone in tanshinones-induced apoptosis in HepG2

Related Experiment Video

Updated: Jun 22, 2026

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration
11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

Wayne Y W Lee1, Ken W K Liu, John H K Yeung

  • 1Department of Pharmacology, The Chinese University of Hong Kong, Shatin, New Territories, SAR, China.

Cancer Letters
|May 27, 2009
PubMed

Insights

Dihydrotanshinone from Salvia miltiorrhiza induces apoptosis in HepG2 cells by generating reactive oxygen species (ROS) and activating p38 mitogen-activated protein kinases (MAPK). This ROS-mediated p38 MAPK pathway is crucial for the observed cell death.

Area of Science:

  • Pharmacology
  • Cell Biology
  • Natural Products Chemistry

Background:

  • Salvia miltiorrhiza contains tanshinones, known for their medicinal properties.
  • Reactive oxygen species (ROS) and p38 mitogen-activated protein kinases (MAPK) are implicated in cellular processes, including apoptosis.
  • Understanding the mechanisms of tanshinone-induced apoptosis is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the role of ROS and p38 MAPK in tanshinone-induced apoptosis in HepG2 cells.
  • To determine the specific mechanisms by which major tanshinones exert their cytotoxic effects.
  • To identify the most potent tanshinone derivative in inducing apoptosis.

Main Methods:

  • HepG2 cells were treated with isolated tanshinones (cryptotanshinone, dihydrotanshinone, tanshinone I, tanshinone IIA).
  • Cell growth inhibition and apoptosis were assessed concentration-dependently.
  • ROS generation and p38 MAPK activation were measured.
  • The effect of N-acetyl cysteine on p38 MAPK activation was evaluated.

Main Results:

  • All four tanshinones inhibited cell growth and induced caspase-dependent apoptosis.
  • Dihydrotanshinone demonstrated the highest potency in inducing apoptosis.
  • All tested tanshinones induced ROS generation.
  • Only dihydrotanshinone activated p38 MAPK, an effect inhibited by N-acetyl cysteine.

Conclusions:

  • Dihydrotanshinone is the most potent tanshinone in inducing apoptosis in HepG2 cells.
  • ROS generation is a common mechanism for tanshinones-induced apoptosis.
  • ROS-mediated p38 MAPK activation is a critical pathway in dihydrotanshinone-induced apoptosis.

More Related Videos

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity09:32

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity

Published on: October 17, 2025

Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
Bioactivation and Tissue Toxicity01:25

Bioactivation and Tissue Toxicity

Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...