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Farnesiferol C Exerts Antiproliferative Effects on Hepatocellular Carcinoma HepG2 Cells by Instigating ROS-Dependent Apoptotic Pathway
Farnesiferol C (Far-C) is a coumarin commonly extracted from Ferula asafetida and is popularly used as a traditional source of natural remedy. Liver cancer or hepatocellular carcinoma (HCC) has emerged as a major cause behind cancer burden, and limited therapeutic interventions have further aggravat...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9501262/ https://www.ncbi.nlm.nih.gov/pubmed/36145291 http://dx.doi.org/10.3390/ph15091070 |
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author | Alafnan, Ahmed Alamri, Abdulwahab Alanazi, Jowaher Hussain, Talib |
author_facet | Alafnan, Ahmed Alamri, Abdulwahab Alanazi, Jowaher Hussain, Talib |
author_sort | Alafnan, Ahmed |
collection | PubMed |
description | Farnesiferol C (Far-C) is a coumarin commonly extracted from Ferula asafetida and is popularly used as a traditional source of natural remedy. Liver cancer or hepatocellular carcinoma (HCC) has emerged as a major cause behind cancer burden, and limited therapeutic interventions have further aggravated the clinical management of HCC. In the present study, the authors tested the hypothesis that Far-C-instigated oxidative stress resulted in anti-proliferation and apoptosis instigation within human liver cancer HepG2 cells. The observations reported herewith indicated that Far-C exerted considerable cytotoxic effects on HepG2 cells by reducing the cell viability (p < 0.001) in a dose-dependent manner. Far-C exposure also resulted in enhanced ROS production (p < 0.01) which subsequently led to loss of mitochondrial membrane potential. Far-C-instigated oxidative stress also led to enhanced nuclear fragmentation and condensation as revealed through Hoechst-33342. These molecular changes post-Far-C exposure also incited apoptotic cell death which concomitantly led to significant activation of caspase-3 (p < 0.001). Furthermore, Far-C exhibited its competence in altering the expression of genes involved in apoptosis regulation (Bax, Bad, and Bcl2) along with genes exerting regulatory effects on cell cycle (cyclinD1) and its progression (p21(Cip1) and CDK4). The evidence thus clearly shows the preclinical efficacy of Far-C against HepG2 cells. However, further mechanistic investigations deciphering the alteration of different pathways post-Far-C exposure will be highly beneficial. |
format | Online Article Text |
id | pubmed-9501262 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95012622022-09-24 Farnesiferol C Exerts Antiproliferative Effects on Hepatocellular Carcinoma HepG2 Cells by Instigating ROS-Dependent Apoptotic Pathway Alafnan, Ahmed Alamri, Abdulwahab Alanazi, Jowaher Hussain, Talib Pharmaceuticals (Basel) Article Farnesiferol C (Far-C) is a coumarin commonly extracted from Ferula asafetida and is popularly used as a traditional source of natural remedy. Liver cancer or hepatocellular carcinoma (HCC) has emerged as a major cause behind cancer burden, and limited therapeutic interventions have further aggravated the clinical management of HCC. In the present study, the authors tested the hypothesis that Far-C-instigated oxidative stress resulted in anti-proliferation and apoptosis instigation within human liver cancer HepG2 cells. The observations reported herewith indicated that Far-C exerted considerable cytotoxic effects on HepG2 cells by reducing the cell viability (p < 0.001) in a dose-dependent manner. Far-C exposure also resulted in enhanced ROS production (p < 0.01) which subsequently led to loss of mitochondrial membrane potential. Far-C-instigated oxidative stress also led to enhanced nuclear fragmentation and condensation as revealed through Hoechst-33342. These molecular changes post-Far-C exposure also incited apoptotic cell death which concomitantly led to significant activation of caspase-3 (p < 0.001). Furthermore, Far-C exhibited its competence in altering the expression of genes involved in apoptosis regulation (Bax, Bad, and Bcl2) along with genes exerting regulatory effects on cell cycle (cyclinD1) and its progression (p21(Cip1) and CDK4). The evidence thus clearly shows the preclinical efficacy of Far-C against HepG2 cells. However, further mechanistic investigations deciphering the alteration of different pathways post-Far-C exposure will be highly beneficial. MDPI 2022-08-28 /pmc/articles/PMC9501262/ /pubmed/36145291 http://dx.doi.org/10.3390/ph15091070 Text en © 2022 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 Alafnan, Ahmed Alamri, Abdulwahab Alanazi, Jowaher Hussain, Talib Farnesiferol C Exerts Antiproliferative Effects on Hepatocellular Carcinoma HepG2 Cells by Instigating ROS-Dependent Apoptotic Pathway |
title | Farnesiferol C Exerts Antiproliferative Effects on Hepatocellular Carcinoma HepG2 Cells by Instigating ROS-Dependent Apoptotic Pathway |
title_full | Farnesiferol C Exerts Antiproliferative Effects on Hepatocellular Carcinoma HepG2 Cells by Instigating ROS-Dependent Apoptotic Pathway |
title_fullStr | Farnesiferol C Exerts Antiproliferative Effects on Hepatocellular Carcinoma HepG2 Cells by Instigating ROS-Dependent Apoptotic Pathway |
title_full_unstemmed | Farnesiferol C Exerts Antiproliferative Effects on Hepatocellular Carcinoma HepG2 Cells by Instigating ROS-Dependent Apoptotic Pathway |
title_short | Farnesiferol C Exerts Antiproliferative Effects on Hepatocellular Carcinoma HepG2 Cells by Instigating ROS-Dependent Apoptotic Pathway |
title_sort | farnesiferol c exerts antiproliferative effects on hepatocellular carcinoma hepg2 cells by instigating ros-dependent apoptotic pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9501262/ https://www.ncbi.nlm.nih.gov/pubmed/36145291 http://dx.doi.org/10.3390/ph15091070 |
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