Cargando…
Fraxetin Suppresses Cell Proliferation and Induces Apoptosis through Mitochondria Dysfunction in Human Hepatocellular Carcinoma Cell Lines Huh7 and Hep3B
Fraxetin is a coumarin scaffold compound extracted from Fraxinus rhynchophylla. It has antioxidant, anti-inflammatory, hepatoprotective, and antifibrotic effects. Furthermore, fraxetin has anticancer effects in breast and lung cancer. We aimed to evaluate whether fraxetin has anticancer activity in...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830088/ https://www.ncbi.nlm.nih.gov/pubmed/33477262 http://dx.doi.org/10.3390/pharmaceutics13010112 |
_version_ | 1783641326342897664 |
---|---|
author | Song, Jisoo Ham, Jiyeon Hong, Taeyeon Song, Gwonhwa Lim, Whasun |
author_facet | Song, Jisoo Ham, Jiyeon Hong, Taeyeon Song, Gwonhwa Lim, Whasun |
author_sort | Song, Jisoo |
collection | PubMed |
description | Fraxetin is a coumarin scaffold compound extracted from Fraxinus rhynchophylla. It has antioxidant, anti-inflammatory, hepatoprotective, and antifibrotic effects. Furthermore, fraxetin has anticancer effects in breast and lung cancer. We aimed to evaluate whether fraxetin has anticancer activity in hepatocellular carcinoma (HCC) cells and its underlying mechanism. We demonstrated the anticancer effects of fraxetin in the HCC cell lines Huh7 and Hep3B. We confirmed that fraxetin inhibited cell proliferation (42% ± 10% Huh7; 52% ± 7% Hep3B) by arresting the cell cycle and inducing apoptosis in both cell lines. Moreover, fraxetin increased reactive oxygen species production (221% ± 55% Huh7; 460% ± 73% Hep3B), depolarized the mitochondrial membranes (ΔΨm) (345% ± 160% Huh7; 462% ± 140% Hep3B), and disrupted calcium homeostasis in both HCC cell lines. Chelating calcium ions with BAPTA-AM restored proliferation in fraxetin-treated Huh7 cells but not in Hep3B cells. Fraxetin did not affect the phosphorylation of extracellular-signal-regulated kinase 1/2, whereas it decreased JNK and phosphoinositide 3-kinase signaling. Furthermore, fraxetin and mitogen-activated protein kinase pharmacological inhibitors had synergistic antiproliferative effects on HCC cells. Although our study was limited to in vitro data that require validation, we suggest that fraxetin is a potential therapeutic agent against HCC progression. |
format | Online Article Text |
id | pubmed-7830088 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78300882021-01-26 Fraxetin Suppresses Cell Proliferation and Induces Apoptosis through Mitochondria Dysfunction in Human Hepatocellular Carcinoma Cell Lines Huh7 and Hep3B Song, Jisoo Ham, Jiyeon Hong, Taeyeon Song, Gwonhwa Lim, Whasun Pharmaceutics Article Fraxetin is a coumarin scaffold compound extracted from Fraxinus rhynchophylla. It has antioxidant, anti-inflammatory, hepatoprotective, and antifibrotic effects. Furthermore, fraxetin has anticancer effects in breast and lung cancer. We aimed to evaluate whether fraxetin has anticancer activity in hepatocellular carcinoma (HCC) cells and its underlying mechanism. We demonstrated the anticancer effects of fraxetin in the HCC cell lines Huh7 and Hep3B. We confirmed that fraxetin inhibited cell proliferation (42% ± 10% Huh7; 52% ± 7% Hep3B) by arresting the cell cycle and inducing apoptosis in both cell lines. Moreover, fraxetin increased reactive oxygen species production (221% ± 55% Huh7; 460% ± 73% Hep3B), depolarized the mitochondrial membranes (ΔΨm) (345% ± 160% Huh7; 462% ± 140% Hep3B), and disrupted calcium homeostasis in both HCC cell lines. Chelating calcium ions with BAPTA-AM restored proliferation in fraxetin-treated Huh7 cells but not in Hep3B cells. Fraxetin did not affect the phosphorylation of extracellular-signal-regulated kinase 1/2, whereas it decreased JNK and phosphoinositide 3-kinase signaling. Furthermore, fraxetin and mitogen-activated protein kinase pharmacological inhibitors had synergistic antiproliferative effects on HCC cells. Although our study was limited to in vitro data that require validation, we suggest that fraxetin is a potential therapeutic agent against HCC progression. MDPI 2021-01-17 /pmc/articles/PMC7830088/ /pubmed/33477262 http://dx.doi.org/10.3390/pharmaceutics13010112 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Song, Jisoo Ham, Jiyeon Hong, Taeyeon Song, Gwonhwa Lim, Whasun Fraxetin Suppresses Cell Proliferation and Induces Apoptosis through Mitochondria Dysfunction in Human Hepatocellular Carcinoma Cell Lines Huh7 and Hep3B |
title | Fraxetin Suppresses Cell Proliferation and Induces Apoptosis through Mitochondria Dysfunction in Human Hepatocellular Carcinoma Cell Lines Huh7 and Hep3B |
title_full | Fraxetin Suppresses Cell Proliferation and Induces Apoptosis through Mitochondria Dysfunction in Human Hepatocellular Carcinoma Cell Lines Huh7 and Hep3B |
title_fullStr | Fraxetin Suppresses Cell Proliferation and Induces Apoptosis through Mitochondria Dysfunction in Human Hepatocellular Carcinoma Cell Lines Huh7 and Hep3B |
title_full_unstemmed | Fraxetin Suppresses Cell Proliferation and Induces Apoptosis through Mitochondria Dysfunction in Human Hepatocellular Carcinoma Cell Lines Huh7 and Hep3B |
title_short | Fraxetin Suppresses Cell Proliferation and Induces Apoptosis through Mitochondria Dysfunction in Human Hepatocellular Carcinoma Cell Lines Huh7 and Hep3B |
title_sort | fraxetin suppresses cell proliferation and induces apoptosis through mitochondria dysfunction in human hepatocellular carcinoma cell lines huh7 and hep3b |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830088/ https://www.ncbi.nlm.nih.gov/pubmed/33477262 http://dx.doi.org/10.3390/pharmaceutics13010112 |
work_keys_str_mv | AT songjisoo fraxetinsuppressescellproliferationandinducesapoptosisthroughmitochondriadysfunctioninhumanhepatocellularcarcinomacelllineshuh7andhep3b AT hamjiyeon fraxetinsuppressescellproliferationandinducesapoptosisthroughmitochondriadysfunctioninhumanhepatocellularcarcinomacelllineshuh7andhep3b AT hongtaeyeon fraxetinsuppressescellproliferationandinducesapoptosisthroughmitochondriadysfunctioninhumanhepatocellularcarcinomacelllineshuh7andhep3b AT songgwonhwa fraxetinsuppressescellproliferationandinducesapoptosisthroughmitochondriadysfunctioninhumanhepatocellularcarcinomacelllineshuh7andhep3b AT limwhasun fraxetinsuppressescellproliferationandinducesapoptosisthroughmitochondriadysfunctioninhumanhepatocellularcarcinomacelllineshuh7andhep3b |