Cargando…

Anti-Proliferative and Anti-Migratory Activities of Hispidulin on Human Melanoma A2058 Cells

Melanoma represents less than 5% of skin cancers, but is the most lethal, mainly because of its high-metastatic potential and resistance to various therapies. Therefore, it is important to develop effective treatments, especially chemotherapeutic drugs with cytotoxicity, anti-metastaticity, and few...

Descripción completa

Detalles Bibliográficos
Autores principales: Chang, Chi-Jen, Hung, Yen-Ling, Chen, Ting-Chen, Li, Hsin-Ju, Lo, Yuan-Hsin, Wu, Nan-Lin, Chang, Der-Chen, Hung, Chi-Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301921/
https://www.ncbi.nlm.nih.gov/pubmed/34356663
http://dx.doi.org/10.3390/biom11071039
_version_ 1783726783576670208
author Chang, Chi-Jen
Hung, Yen-Ling
Chen, Ting-Chen
Li, Hsin-Ju
Lo, Yuan-Hsin
Wu, Nan-Lin
Chang, Der-Chen
Hung, Chi-Feng
author_facet Chang, Chi-Jen
Hung, Yen-Ling
Chen, Ting-Chen
Li, Hsin-Ju
Lo, Yuan-Hsin
Wu, Nan-Lin
Chang, Der-Chen
Hung, Chi-Feng
author_sort Chang, Chi-Jen
collection PubMed
description Melanoma represents less than 5% of skin cancers, but is the most lethal, mainly because of its high-metastatic potential and resistance to various therapies. Therefore, it is important to develop effective treatments, especially chemotherapeutic drugs with cytotoxicity, anti-metastaticity, and few side effects. One such natural product is hispidulin, a flavone distributed in plants of the Asteraceae. Previous studies have demonstrated that hispidulin has various pharmacological benefits, such as anti-tumor, anti-inflammation, and anti-allergic effects. This study aims to explore the effects of hispidulin against melanoma in vitro and in vivo. Results revealed that hispidulin selectively decreased the cell viability of A2058 cells in a dose- and time-dependent manner. Hispidulin induced cells accumulated in the sub-G1 phase via activating caspase 8 and 9, increased cleaved caspase 3, and cleaved PARP expression. Hispidulin was able to decrease AKT and ERK phosphorylation, which facilitated cell growth and survival. Moreover, hispidulin promoted reactive oxygen species generation in cells and suppressed cell migration through downregulated matrix metalloproteinase-2 expression. Hispidulin significantly inhibited tumor growth in a xenograft model. Based on these results, hispidulin produces its anti-melanoma effects by inducing cancer cell apoptosis and reducing its migration. Therefore, we suggest hispidulin as a potent therapeutic candidate for melanoma treatment.
format Online
Article
Text
id pubmed-8301921
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83019212021-07-24 Anti-Proliferative and Anti-Migratory Activities of Hispidulin on Human Melanoma A2058 Cells Chang, Chi-Jen Hung, Yen-Ling Chen, Ting-Chen Li, Hsin-Ju Lo, Yuan-Hsin Wu, Nan-Lin Chang, Der-Chen Hung, Chi-Feng Biomolecules Article Melanoma represents less than 5% of skin cancers, but is the most lethal, mainly because of its high-metastatic potential and resistance to various therapies. Therefore, it is important to develop effective treatments, especially chemotherapeutic drugs with cytotoxicity, anti-metastaticity, and few side effects. One such natural product is hispidulin, a flavone distributed in plants of the Asteraceae. Previous studies have demonstrated that hispidulin has various pharmacological benefits, such as anti-tumor, anti-inflammation, and anti-allergic effects. This study aims to explore the effects of hispidulin against melanoma in vitro and in vivo. Results revealed that hispidulin selectively decreased the cell viability of A2058 cells in a dose- and time-dependent manner. Hispidulin induced cells accumulated in the sub-G1 phase via activating caspase 8 and 9, increased cleaved caspase 3, and cleaved PARP expression. Hispidulin was able to decrease AKT and ERK phosphorylation, which facilitated cell growth and survival. Moreover, hispidulin promoted reactive oxygen species generation in cells and suppressed cell migration through downregulated matrix metalloproteinase-2 expression. Hispidulin significantly inhibited tumor growth in a xenograft model. Based on these results, hispidulin produces its anti-melanoma effects by inducing cancer cell apoptosis and reducing its migration. Therefore, we suggest hispidulin as a potent therapeutic candidate for melanoma treatment. MDPI 2021-07-16 /pmc/articles/PMC8301921/ /pubmed/34356663 http://dx.doi.org/10.3390/biom11071039 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
Chang, Chi-Jen
Hung, Yen-Ling
Chen, Ting-Chen
Li, Hsin-Ju
Lo, Yuan-Hsin
Wu, Nan-Lin
Chang, Der-Chen
Hung, Chi-Feng
Anti-Proliferative and Anti-Migratory Activities of Hispidulin on Human Melanoma A2058 Cells
title Anti-Proliferative and Anti-Migratory Activities of Hispidulin on Human Melanoma A2058 Cells
title_full Anti-Proliferative and Anti-Migratory Activities of Hispidulin on Human Melanoma A2058 Cells
title_fullStr Anti-Proliferative and Anti-Migratory Activities of Hispidulin on Human Melanoma A2058 Cells
title_full_unstemmed Anti-Proliferative and Anti-Migratory Activities of Hispidulin on Human Melanoma A2058 Cells
title_short Anti-Proliferative and Anti-Migratory Activities of Hispidulin on Human Melanoma A2058 Cells
title_sort anti-proliferative and anti-migratory activities of hispidulin on human melanoma a2058 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301921/
https://www.ncbi.nlm.nih.gov/pubmed/34356663
http://dx.doi.org/10.3390/biom11071039
work_keys_str_mv AT changchijen antiproliferativeandantimigratoryactivitiesofhispidulinonhumanmelanomaa2058cells
AT hungyenling antiproliferativeandantimigratoryactivitiesofhispidulinonhumanmelanomaa2058cells
AT chentingchen antiproliferativeandantimigratoryactivitiesofhispidulinonhumanmelanomaa2058cells
AT lihsinju antiproliferativeandantimigratoryactivitiesofhispidulinonhumanmelanomaa2058cells
AT loyuanhsin antiproliferativeandantimigratoryactivitiesofhispidulinonhumanmelanomaa2058cells
AT wunanlin antiproliferativeandantimigratoryactivitiesofhispidulinonhumanmelanomaa2058cells
AT changderchen antiproliferativeandantimigratoryactivitiesofhispidulinonhumanmelanomaa2058cells
AT hungchifeng antiproliferativeandantimigratoryactivitiesofhispidulinonhumanmelanomaa2058cells