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In Vitro Cell Density Determines the Sensitivity of Hepatocarcinoma Cells to Ascorbate

Hepatocellular carcinoma (HCC) is the primary histological subtype of liver cancer, and its incidence rates increase with age. Recently, systemic therapies, such as immune checkpoint inhibitors, monoclonal antibodies, and tyrosine kinase inhibitors (TKIs), have been more beneficial than conventional...

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Autores principales: Fan, Hsiu-Lung, Liu, Shu-Ting, Chang, Yung-Lung, Chiu, Yi-Lin, Huang, Shih-Ming, Chen, Teng-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169715/
https://www.ncbi.nlm.nih.gov/pubmed/35677156
http://dx.doi.org/10.3389/fonc.2022.843742
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author Fan, Hsiu-Lung
Liu, Shu-Ting
Chang, Yung-Lung
Chiu, Yi-Lin
Huang, Shih-Ming
Chen, Teng-Wei
author_facet Fan, Hsiu-Lung
Liu, Shu-Ting
Chang, Yung-Lung
Chiu, Yi-Lin
Huang, Shih-Ming
Chen, Teng-Wei
author_sort Fan, Hsiu-Lung
collection PubMed
description Hepatocellular carcinoma (HCC) is the primary histological subtype of liver cancer, and its incidence rates increase with age. Recently, systemic therapies, such as immune checkpoint inhibitors, monoclonal antibodies, and tyrosine kinase inhibitors (TKIs), have been more beneficial than conventional therapies for treating HCC. Nonetheless, the prognosis of late-stage HCC remains dismal because of its high recurrence rates, even with substantial advances in current therapeutic strategies. A new treatment, such as a combination of current systemic therapies, is urgently required. Therefore, we adopted a repurposing strategy and tried to combine ascorbate with TKIs, including lenvatinib and regorafenib, in HepG2 and Hep3B cells. We investigated the potential functional impact of pharmacological concentrations of ascorbate on the cell-cycle profiles, mitochondrial membrane potential, oxidative response, synergistic effects of lenvatinib or regorafenib, and differential responsiveness between HepG2 and Hep3B cells. Our data suggest that the relative level of cell density is an important determinant for ascorbate cytotoxicity in HCC. Furthermore, the data also revealed that the cytotoxic effect of pharmacological concentrations of ascorbate might not be mediated via our proposed elevation of ROS generation. Ascorbate might be involved in redox homeostasis to enhance the efficacy of TKIs in HepG2 and Hep3B cells. The synergistic effects of ascorbate with TKIs (lenvatinib and regorafenib) support their potential as an adjuvant for HCC targeted TKI therapy. This research provides a cheap and new combinatory therapy for HCC treatment.
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spelling pubmed-91697152022-06-07 In Vitro Cell Density Determines the Sensitivity of Hepatocarcinoma Cells to Ascorbate Fan, Hsiu-Lung Liu, Shu-Ting Chang, Yung-Lung Chiu, Yi-Lin Huang, Shih-Ming Chen, Teng-Wei Front Oncol Oncology Hepatocellular carcinoma (HCC) is the primary histological subtype of liver cancer, and its incidence rates increase with age. Recently, systemic therapies, such as immune checkpoint inhibitors, monoclonal antibodies, and tyrosine kinase inhibitors (TKIs), have been more beneficial than conventional therapies for treating HCC. Nonetheless, the prognosis of late-stage HCC remains dismal because of its high recurrence rates, even with substantial advances in current therapeutic strategies. A new treatment, such as a combination of current systemic therapies, is urgently required. Therefore, we adopted a repurposing strategy and tried to combine ascorbate with TKIs, including lenvatinib and regorafenib, in HepG2 and Hep3B cells. We investigated the potential functional impact of pharmacological concentrations of ascorbate on the cell-cycle profiles, mitochondrial membrane potential, oxidative response, synergistic effects of lenvatinib or regorafenib, and differential responsiveness between HepG2 and Hep3B cells. Our data suggest that the relative level of cell density is an important determinant for ascorbate cytotoxicity in HCC. Furthermore, the data also revealed that the cytotoxic effect of pharmacological concentrations of ascorbate might not be mediated via our proposed elevation of ROS generation. Ascorbate might be involved in redox homeostasis to enhance the efficacy of TKIs in HepG2 and Hep3B cells. The synergistic effects of ascorbate with TKIs (lenvatinib and regorafenib) support their potential as an adjuvant for HCC targeted TKI therapy. This research provides a cheap and new combinatory therapy for HCC treatment. Frontiers Media S.A. 2022-05-23 /pmc/articles/PMC9169715/ /pubmed/35677156 http://dx.doi.org/10.3389/fonc.2022.843742 Text en Copyright © 2022 Fan, Liu, Chang, Chiu, Huang and Chen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Fan, Hsiu-Lung
Liu, Shu-Ting
Chang, Yung-Lung
Chiu, Yi-Lin
Huang, Shih-Ming
Chen, Teng-Wei
In Vitro Cell Density Determines the Sensitivity of Hepatocarcinoma Cells to Ascorbate
title In Vitro Cell Density Determines the Sensitivity of Hepatocarcinoma Cells to Ascorbate
title_full In Vitro Cell Density Determines the Sensitivity of Hepatocarcinoma Cells to Ascorbate
title_fullStr In Vitro Cell Density Determines the Sensitivity of Hepatocarcinoma Cells to Ascorbate
title_full_unstemmed In Vitro Cell Density Determines the Sensitivity of Hepatocarcinoma Cells to Ascorbate
title_short In Vitro Cell Density Determines the Sensitivity of Hepatocarcinoma Cells to Ascorbate
title_sort in vitro cell density determines the sensitivity of hepatocarcinoma cells to ascorbate
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169715/
https://www.ncbi.nlm.nih.gov/pubmed/35677156
http://dx.doi.org/10.3389/fonc.2022.843742
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