Research Papers:

Immunonutritional consequences of different serine-type protease inhibitors in a C57BL/6 hepatocarcinoma model

Jose Laparra _, Bartosz Fotschki and Claudia Haros

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Oncotarget. 2019; 10:760-772. https://doi.org/10.18632/oncotarget.26605

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Jose Laparra1, Bartosz Fotschki2 and Claudia Haros3

1Madrid Institute for Advanced studies in Food (IMDEA Food), Ctra, 28049 Madrid, Spain

2Department of Biological Function of Food, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland

3Instituto de Agroquímica y Tecnología de Alimentos (IATA), Consejo Superior de Investigaciones Científicas (CSIC), Parque Científico, Paterna, 46980 Valencia, Spain

Correspondence to:

Jose Laparra, email: [email protected]

Keywords: hepatocarcinoma; serine-type protease inhibitors; macrophage; innate immunity; immunonutrition

Received: November 13, 2018     Accepted: January 09, 2019     Published: January 22, 2019


Imbalances in innate immunity and the activity of innate immune cells are implicated in the development of hepatocellular carcinoma (HCC). Plant seeds are good sources of protease inhibitors, which can have a significant influence on human health disorders, especially in the field of cancer prevention. To elucidate the impact and preventive effects of immunonutritional serine-type protease inhibitors (STPIs) on HCC, it was used an established model of chemically induced liver injury. Injured livers induced Akt as well as hepatic infiltration of NKG2D+ and CD74+ cells. Feeding STPIs reduced size and number of intrahepatic nodes of mononuclear. These animals showed an inverse association of the severity of HCC with bioactive hepcidin levels, which was significantly correlated with the hepatic myeloperoxidase activity. According to their origin, administration of STPIs significantly induce increased numbers of F4/80+ cells in injured livers that can be responsible for the biological effects detected on the parenchyma and inflammatory markers under DEN/TAA treatment. These findings can have direct implications in HCC immunotherapy where enhanced response(s) in inflammation-driven cancer patients could help promoting inflammation-driven processes and favor tumor growth. Altogether, this study demonstrates that oral administration of STPIs modulate innate immunity response influencing HCC aggressiveness and progression. These results represent a path forward to develop durable, long-lasting response against hepatocarcinoma and open a future research path in the development of coadjutant intervention strategies to pharmacological therapies.

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