Unraveling the impact of melatonin treatment: Oxidative stress, metabolic responses, and morphological changes in HuH7.5 hepatocellular carcinoma cells.

Autor: de Morais JMB; Laboratory of Immunoparasitology of Neglected Diseases and Cancer, State University of Londrina (UEL), PR, Brazil., Cruz EMS; Laboratory of Immunoparasitology of Neglected Diseases and Cancer, State University of Londrina (UEL), PR, Brazil., Concato VM; Laboratory of Immunoparasitology of Neglected Diseases and Cancer, State University of Londrina (UEL), PR, Brazil., de Souza MC; North of Paraná State University (UENP), Biological Science Center, Bandeirantes, PR, Brazil., Santos YM; Laboratory of Immunoparasitology of Neglected Diseases and Cancer, State University of Londrina (UEL), PR, Brazil., Quadreli DH; General Biology Department, Biological Sciences Center, State University of Londrina, Londrina (UEL), PR, Brazil., Inoue FSR; Laboratory of Immunoparasitology of Neglected Diseases and Cancer, State University of Londrina (UEL), PR, Brazil., Ferreira FB; North of Paraná State University (UENP), Biological Science Center, Bandeirantes, PR, Brazil., Fernandes GSA; General Biology Department, Biological Sciences Center, State University of Londrina, Londrina (UEL), PR, Brazil., Bidóia DL; State University of Maringá (UEM), Maringá, PR, Brazil., Machado RRB; State University of Maringá (UEM), Maringá, PR, Brazil., Chuffa LGA; Department of Structural and Functional Biology, São Paulo State University (UNESP), Institute of Bioscience, Botucatu, SP, Brazil., Pavanelli WR; Laboratory of Immunoparasitology of Neglected Diseases and Cancer, State University of Londrina (UEL), PR, Brazil., Seiva FRF; Department of Chemical and Biological Sciences, São Paulo State University (UNESP), Institute of Bioscience, Botucatu, SP, Brazil. Electronic address: fabio.seiva@unesp.br.
Jazyk: angličtina
Zdroj: Pathology, research and practice [Pathol Res Pract] 2024 Jan; Vol. 253, pp. 155056. Date of Electronic Publication: 2023 Dec 21.
DOI: 10.1016/j.prp.2023.155056
Abstrakt: In addition to its highly aggressive nature and late diagnosis, hepatocellular carcinoma (HCC) does not respond effectively to available chemotherapeutic agents. The search is on for an ideal and effective compound with low cost and minimal side effects that can be used as an adjunct to chemotherapeutic regimens. One of the mechanisms involved in the pathology of HCC is the oxidative stress, which plays a critical role in tumor survival and dissemination. Our group has already demonstrated the antitumor potential of melatonin against HuH 7.5 cells. In the present study, we focused on the effects of melatonin on oxidative stress parameters and their consequences on cell metabolism. HuH 7.5 cells were treated with 2 and 4 mM of melatonin for 24 and 48 h. Oxidative stress biomarkers, antioxidant enzyme, mitochondrial membrane potential, formation of lipid bodies and autophagic vacuoles, cell cycle progression, cell death rate and ultrastructural cell alterations were evaluated. The treatment with melatonin increased oxidative stress biomarkers and reduced antioxidant enzyme activities of HuH 7.5 cells. Additionally, melatonin treatment damaged the mitochondrial membrane and increased lipid bodies and autophagic vacuole formation. Melatonin triggered cell cycle arrest and induced cell death by apoptosis. Our results indicate that the treatment of HuH 7.5 cells with melatonin impaired antioxidant defense systems, inhibited cell cycle progression, and caused metabolic stress, culminating in tumor cell death.
Competing Interests: Declaration of Competing Interest All co-authors have contributed substantially to conducting the underlying research and drafting this manuscript.The authors of this manuscript declare that they have no conflict of interest.
(Copyright © 2024 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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