Chitinase boosts endoplasmic reticulum stress and triggers apoptosis and autophagy in a hepatocellular carcinoma rat model

Abstract

Objective: To assess the antitumor activity of the novel chitinase produced by fermented, isolated Trichoderma viride in a hepatocellular carcinoma (HCC) male rat model.

Methods: Diethyl-nitrosamine induction combined with ionizing radiation exposure was used to establish the HCC rat model. All rats were divided into 4 groups: the control group, the chitinase group, the HCC group, and the HCC + chitinase group. The antiproliferative effect of chitinase was evaluated in human HCC cells. The effect of chitinase in vivo on oxidative stress, endoplasmic reticulum stress chaperones, autophagy markers, PI3K/AKT/mTOR, AMPK pathway expression, and apoptotic indicators was determined and confirmed by histological examination.

Results: Chitinase significantly inhibited the viabilities of HepG2 cells. Moreover, in the Wistar male rat model of HCC, chitinase decreased ATP levels, modulated endoplasmic reticulum stress, mediated autophagy factors, and promoted apoptosis.

Conclusions: Chitinase might play a role in the apoptosis as well as autophagy pathways and may act as a potential tumor suppressor.

Keywords

Trichoderma viride / Chitinase / Hepatocellular carcinoma / ER stress / Apoptosis / Autophagy / PI3K/AKT/mTOR / AMPK

Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

The article received no extramural funding.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Authors’ contributions

AIN, FSMM, and EMM contributed to the conceptualization, research design, implementation of the research, analysis of the results, and writing of the manuscript.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Acknowledgments

The authors express gratitude to Dr. Medhat Ahmed Abu-Tahon and Dr. George Saad Isaac of the Biological and Geological Sciences Department, Faculty of Education, Ain Shams University, Heliopolis, Cairo, Egypt, for generously supplying chitinase and its characterization. We appreciate the help from Dr. Osama M. Mostafa, a lecturer in histopathology at Al-Azhar University's Faculty of Medicine, in analyzing histopathology.

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