Cargando…

Anticancer Activities of Hesperidin via Suppression of Up-Regulated Programmed Death-Ligand 1 Expression in Oral Cancer Cells

Up-regulated expression of programmed death-ligand 1 (PD-L1) by interferon-gamma (IFN-γ) has been associated with promotion of cancer cell survival and tumor cell escape from anti-tumor immunity. Therefore, a blockade of PD-L1 expression can potentially be used as a molecular target for cancer thera...

Descripción completa

Detalles Bibliográficos
Autores principales: Wudtiwai, Benjawan, Makeudom, Anupong, Krisanaprakornkit, Suttichai, Pothacharoen, Peraphan, Kongtawelert, Prachya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434411/
https://www.ncbi.nlm.nih.gov/pubmed/34500779
http://dx.doi.org/10.3390/molecules26175345
_version_ 1783751593291677696
author Wudtiwai, Benjawan
Makeudom, Anupong
Krisanaprakornkit, Suttichai
Pothacharoen, Peraphan
Kongtawelert, Prachya
author_facet Wudtiwai, Benjawan
Makeudom, Anupong
Krisanaprakornkit, Suttichai
Pothacharoen, Peraphan
Kongtawelert, Prachya
author_sort Wudtiwai, Benjawan
collection PubMed
description Up-regulated expression of programmed death-ligand 1 (PD-L1) by interferon-gamma (IFN-γ) has been associated with promotion of cancer cell survival and tumor cell escape from anti-tumor immunity. Therefore, a blockade of PD-L1 expression can potentially be used as a molecular target for cancer therapy. The aim of this study was to investigate whether suppression of IFN-γ induced PD-L1 expression in two oral cancer cell lines, HN6 and HN15, by hesperidin effectively decreased cell proliferation and migration. Further, our objective was to elucidate the involvement of the signal transducer and activator of transcription 1 (STAT1) and STAT3 in the inhibition of induced PD-L1 expression by hesperidin. Our findings indicate that IFN-γ induced expression of PD-L1 protein in HN6 and HN15 via phosphorylation of STAT1 and STAT3 and that hesperidin significantly reduced that induction through suppression of phosphorylated STAT1 and STAT3 in both cell lines. Moreover, hesperidin also significantly decreased the viability, proliferation, migration, and invasion of both cell lines. In conclusion, hesperidin exerted anticancer effects against oral cancer cells through the suppression of PD-L1 expression via inactivation of the STAT1 and STAT3 signaling molecules. The findings of this study support the use of hesperidin as a potential adjunctive treatment for oral cancer.
format Online
Article
Text
id pubmed-8434411
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-84344112021-09-12 Anticancer Activities of Hesperidin via Suppression of Up-Regulated Programmed Death-Ligand 1 Expression in Oral Cancer Cells Wudtiwai, Benjawan Makeudom, Anupong Krisanaprakornkit, Suttichai Pothacharoen, Peraphan Kongtawelert, Prachya Molecules Article Up-regulated expression of programmed death-ligand 1 (PD-L1) by interferon-gamma (IFN-γ) has been associated with promotion of cancer cell survival and tumor cell escape from anti-tumor immunity. Therefore, a blockade of PD-L1 expression can potentially be used as a molecular target for cancer therapy. The aim of this study was to investigate whether suppression of IFN-γ induced PD-L1 expression in two oral cancer cell lines, HN6 and HN15, by hesperidin effectively decreased cell proliferation and migration. Further, our objective was to elucidate the involvement of the signal transducer and activator of transcription 1 (STAT1) and STAT3 in the inhibition of induced PD-L1 expression by hesperidin. Our findings indicate that IFN-γ induced expression of PD-L1 protein in HN6 and HN15 via phosphorylation of STAT1 and STAT3 and that hesperidin significantly reduced that induction through suppression of phosphorylated STAT1 and STAT3 in both cell lines. Moreover, hesperidin also significantly decreased the viability, proliferation, migration, and invasion of both cell lines. In conclusion, hesperidin exerted anticancer effects against oral cancer cells through the suppression of PD-L1 expression via inactivation of the STAT1 and STAT3 signaling molecules. The findings of this study support the use of hesperidin as a potential adjunctive treatment for oral cancer. MDPI 2021-09-02 /pmc/articles/PMC8434411/ /pubmed/34500779 http://dx.doi.org/10.3390/molecules26175345 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wudtiwai, Benjawan
Makeudom, Anupong
Krisanaprakornkit, Suttichai
Pothacharoen, Peraphan
Kongtawelert, Prachya
Anticancer Activities of Hesperidin via Suppression of Up-Regulated Programmed Death-Ligand 1 Expression in Oral Cancer Cells
title Anticancer Activities of Hesperidin via Suppression of Up-Regulated Programmed Death-Ligand 1 Expression in Oral Cancer Cells
title_full Anticancer Activities of Hesperidin via Suppression of Up-Regulated Programmed Death-Ligand 1 Expression in Oral Cancer Cells
title_fullStr Anticancer Activities of Hesperidin via Suppression of Up-Regulated Programmed Death-Ligand 1 Expression in Oral Cancer Cells
title_full_unstemmed Anticancer Activities of Hesperidin via Suppression of Up-Regulated Programmed Death-Ligand 1 Expression in Oral Cancer Cells
title_short Anticancer Activities of Hesperidin via Suppression of Up-Regulated Programmed Death-Ligand 1 Expression in Oral Cancer Cells
title_sort anticancer activities of hesperidin via suppression of up-regulated programmed death-ligand 1 expression in oral cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434411/
https://www.ncbi.nlm.nih.gov/pubmed/34500779
http://dx.doi.org/10.3390/molecules26175345
work_keys_str_mv AT wudtiwaibenjawan anticanceractivitiesofhesperidinviasuppressionofupregulatedprogrammeddeathligand1expressioninoralcancercells
AT makeudomanupong anticanceractivitiesofhesperidinviasuppressionofupregulatedprogrammeddeathligand1expressioninoralcancercells
AT krisanaprakornkitsuttichai anticanceractivitiesofhesperidinviasuppressionofupregulatedprogrammeddeathligand1expressioninoralcancercells
AT pothacharoenperaphan anticanceractivitiesofhesperidinviasuppressionofupregulatedprogrammeddeathligand1expressioninoralcancercells
AT kongtawelertprachya anticanceractivitiesofhesperidinviasuppressionofupregulatedprogrammeddeathligand1expressioninoralcancercells