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Myricetin Selectively Induces Apoptosis on Cancerous Hepatocytes by Directly Targeting Their Mitochondria

Enayatollah Seydi1, Hamid Reza Rasekh1, Ahmad Salimi1,2

  • 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Basic & Clinical Pharmacology & Toxicology
|February 27, 2016
PubMed

Insights

Myricetin selectively induces apoptosis in liver cancer cells, not healthy ones. This flavonoid shows promise as a novel therapeutic agent for hepatocellular carcinoma (HCC) treatment.

Area of Science:

  • Hepatocellular carcinoma (HCC) research
  • Molecular biology
  • Cancer therapy

Background:

  • Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality with limited effective treatments.
  • Current HCC therapies often have poor tolerance and low efficacy, necessitating novel therapeutic strategies.
  • Flavonoids, like myricetin (MYR), are being investigated for their potential anti-cancer properties.

Purpose of the Study:

  • To evaluate the selective apoptotic effects of myricetin (MYR) on hepatocytes and mitochondria in a rat model of hepatocellular carcinoma (HCC).
  • To investigate the underlying mechanisms of MYR-induced apoptosis in cancerous versus normal liver cells.

Main Methods:

  • Hepatocellular carcinoma (HCC) was induced in rats using diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF).
  • Serum markers (alpha-fetoprotein, AST, ALP) and histopathology confirmed HCC induction.
  • Isolated hepatocytes and mitochondria were treated with MYR to assess cytotoxicity, reactive oxygen species (ROS) levels, mitochondrial swelling, membrane permeabilization (MMP), and cytochrome c release.
  • Caspase-3 activation and apoptotic phenotypes were analyzed.

Main Results:

  • Myricetin (MYR) demonstrated selective cytotoxicity, inducing apoptosis only in HCC hepatocytes, not in normal hepatocytes.
  • MYR treatment significantly increased reactive oxygen species (ROS) production, mitochondrial swelling, and cytochrome c release in HCC mitochondria.
  • MYR selectively promoted caspase-3 activation and apoptotic phenotypes in cancerous hepatocytes compared to normal ones.

Conclusions:

  • Myricetin (MYR) exhibits selective apoptotic effects on hepatocellular carcinoma (HCC) cells, sparing normal hepatocytes.
  • MYR induces apoptosis through mechanisms involving mitochondrial dysfunction and caspase-3 activation in HCC.
  • Myricetin is a promising therapeutic candidate for HCC, warranting further investigation.

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