Early fibrosis inhibits hepatocellular carcinoma mediated by free radical effects

Nidal Muhanna, Sarit Doron, Lina Abu-Tair, Hiba Zayyad, Mahmud Mahamid, Johnny Amer, Rifaat Safadi

Research output: Contribution to journalArticlepeer-review

Abstract

We studied the in-vitro/. in-vivo interactions between HCC/HSCs in early and advanced fibrosis-models. Hep3B-mono-cultures secreted high levels of αFetoProtein (αFP). Human-HSCs co-cultured with Hep3B-cells significantly decreased αFP and increased their apoptosis. Confocal-microscopy demonstrated Hep3B-phagocytosis inside the HSCs suggesting a direct cellular-contact mediating anti-tumor effect. Leptin-activated HSCs further suppressed Hep3B-cells with increased ROS and decreased GSH. Following intrahepatic-Hep3B-cell injections, mice with established "advanced liver-fibrosis"; had higher tumor-size and αFP serum-levels as compared to non-fibrotic livers. Mice with "early liver-fibrosis", which initiated post tumor induction had a significant decrease in tumor and high Malondialdehyde (MDA) serum levels compared to advanced-fibrosis animals.At early-fibrosis stages, activated-HSCs express direct anti-tumor effects by phagocytosis and apoptosis of tumor-cells mediated by oxidative stress.

Original languageEnglish
Pages (from-to)391-398
Number of pages8
JournalMitochondrion
Volume13
Issue number5
DOIs
StatePublished - Sep 2013
Externally publishedYes

Keywords

  • Cirrhosis
  • Free radicals
  • Hep3B cells
  • Hepatic fibrosis
  • Homeostasis
  • Phagocytosis

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