Title:Selective Toxicity of Apigenin on Cancerous Hepatocytes by Directly Targeting their Mitochondria
Volume: 16
Issue: 12
Author(s): Enayatollah Seydi, Hamid R. Rasekh, Ahmad Salimi, Zhaleh Mohsenifar and Jalal Pourahmad
Affiliation:
Keywords:
Apigenin, apoptosis, hepatocytes, mitochondria, hepatocellular carcinoma.
Abstract: Background: hepatocellular carcinoma (HCC) is the third cause of mortality due to
cancer throughout the world.
Objective: The main goal of the current research was to evaluate the selective toxicity of
apigenin (APG) on hepatocytes and mitochondria obtained from the liver of HCC rats).
Method: In this research, HCC induced by a single dose of diethylnitrosamine (DEN); 200
mg/kg, i.p, and 2-acetylaminofluorene (2-AAF) (0.02%, through dietary) for 14 days. For
confirmation of HCC, histopathological evaluations and determination of serum concentrations
of liver toxicity enzymes and specific liver cancer marker; alpha-fetoprotein (AFP) were
performed. Then, cancerous and non- cancerous hepatocytes were isolated by using the collagen
perfusion method. Eventually, mitochondria isolated from HCC and normal hepatocytes were
tested for every eventual toxic effects of APG.
Results: After confirmation of HCC, the results of this research showed that APG (10, 20 and 40 μM) increased
mitochondrial parameters such as, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) level,
mitochondrial swelling and cytochrome c expulsion only in cancerous hepatocytes. Apoptotic effect of APG on HCC
cells was confirmed by caspase-3 activation and Annexin V-FITC and PI double staining analysis.
Conclusion: These results propose the eligibility of the flavonoid APG as a complementary therapeutic agent for
patients with hepatocellular carcinoma.
