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

doi:10.1016/j.mito.2013.01.001

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 journal › Article › peer-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 language	English
Pages (from-to)	391-398
Number of pages	8
Journal	Mitochondrion
Volume	13
Issue number	5
DOIs	https://doi.org/10.1016/j.mito.2013.01.001
State	Published - Sep 2013
Externally published	Yes

Keywords

Cirrhosis
Free radicals
Hep3B cells
Hepatic fibrosis
Homeostasis
Phagocytosis

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10.1016/j.mito.2013.01.001

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title = "Early fibrosis inhibits hepatocellular carcinoma mediated by free radical effects",

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.",

keywords = "Cirrhosis, Free radicals, Hep3B cells, Hepatic fibrosis, Homeostasis, Phagocytosis",

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

note = "Funding Information: This study was supported (in part) by grant no. 35937 from the Chief Scientist Office of the Ministry of Health, Israel and by the Israel Science Foundation grant no. 1169/09 . ",

year = "2013",

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doi = "10.1016/j.mito.2013.01.001",

language = "אנגלית",

volume = "13",

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AU - Muhanna, Nidal

AU - Doron, Sarit

AU - Abu-Tair, Lina

AU - Zayyad, Hiba

AU - Mahamid, Mahmud

AU - Amer, Johnny

AU - Safadi, Rifaat

N1 - Funding Information: This study was supported (in part) by grant no. 35937 from the Chief Scientist Office of the Ministry of Health, Israel and by the Israel Science Foundation grant no. 1169/09 .

PY - 2013/9

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N2 - 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.

AB - 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.

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KW - Free radicals

KW - Hep3B cells

KW - Hepatic fibrosis

KW - Homeostasis

KW - Phagocytosis

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Early fibrosis inhibits hepatocellular carcinoma mediated by free radical effects

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Keywords

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