Cargando…

Silibinin Therapy Improves Cholangiocarcinoma Outcomes by Regulating ERK/Mitochondrial Pathway

Background: Silibinin is widely utilized drug in various cancer treatments, though its application in cholangiocarcinoma has not yet been explored. For the first time, we evaluated the anticancer potential and underlying molecular mechanism of silibinin in treatment of cholangiocarcinoma treatment....

Descripción completa

Detalles Bibliográficos
Autores principales: Bai, Yang, Chen, Jiaqi, Hu, Weijian, Wang, Lei, Wu, Yulian, Yu, Shi’an
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983842/
https://www.ncbi.nlm.nih.gov/pubmed/35401195
http://dx.doi.org/10.3389/fphar.2022.847905
_version_ 1784682045739368448
author Bai, Yang
Chen, Jiaqi
Hu, Weijian
Wang, Lei
Wu, Yulian
Yu, Shi’an
author_facet Bai, Yang
Chen, Jiaqi
Hu, Weijian
Wang, Lei
Wu, Yulian
Yu, Shi’an
author_sort Bai, Yang
collection PubMed
description Background: Silibinin is widely utilized drug in various cancer treatments, though its application in cholangiocarcinoma has not yet been explored. For the first time, we evaluated the anticancer potential and underlying molecular mechanism of silibinin in treatment of cholangiocarcinoma treatment. Methods: HuCCT-1 and CCLP-1 cells were chosen to be an in vitro study model and were exposed to various concentrations of silibinin for indicated times. Cell viability was evaluated by the cell counting kit-8 (CCK-8) assay and half maximal inhibitory (IC50) concentrations were calculated. Cell proliferation capacity was determined through the use of colony formation and 5-Ethynyl-2′- deoxyuridine (EdU) assays. Cell apoptosis and cycle arrest were assessed by Live/Dead staining assay and flow cytometry (FCM). The protein levels of extracellular regulated protein kinases (ERK)/mitochondrial apoptotic pathway were evaluated through western blotting (WB). Mitochondrial membrane potential changes were determined via 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1). A cholangiocarcinoma cell line xenograft model was used to assess the anti-tumor activity of silibinin in vivo. Results: Inhibition of the ERK protein by silibinin led to a significant decrease in mitochondrial membrane potential, which, in turn, caused Cytochrome C to be released from the mitochondria. The activation of downstream apoptotic pathways led to apoptosis of cholangiocarcinoma cells. In general, silibinin inhibited the growth of cholangiocarcinoma cell line xenograft tumors. Conclusions: Silibinin is able to inhibit cholangiocarcinoma through the ERK/mitochondrial apoptotic pathway, which makes silibinin a potential anti-tumor drug candidate for cholangiocarcinoma treatment.
format Online
Article
Text
id pubmed-8983842
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-89838422022-04-07 Silibinin Therapy Improves Cholangiocarcinoma Outcomes by Regulating ERK/Mitochondrial Pathway Bai, Yang Chen, Jiaqi Hu, Weijian Wang, Lei Wu, Yulian Yu, Shi’an Front Pharmacol Pharmacology Background: Silibinin is widely utilized drug in various cancer treatments, though its application in cholangiocarcinoma has not yet been explored. For the first time, we evaluated the anticancer potential and underlying molecular mechanism of silibinin in treatment of cholangiocarcinoma treatment. Methods: HuCCT-1 and CCLP-1 cells were chosen to be an in vitro study model and were exposed to various concentrations of silibinin for indicated times. Cell viability was evaluated by the cell counting kit-8 (CCK-8) assay and half maximal inhibitory (IC50) concentrations were calculated. Cell proliferation capacity was determined through the use of colony formation and 5-Ethynyl-2′- deoxyuridine (EdU) assays. Cell apoptosis and cycle arrest were assessed by Live/Dead staining assay and flow cytometry (FCM). The protein levels of extracellular regulated protein kinases (ERK)/mitochondrial apoptotic pathway were evaluated through western blotting (WB). Mitochondrial membrane potential changes were determined via 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1). A cholangiocarcinoma cell line xenograft model was used to assess the anti-tumor activity of silibinin in vivo. Results: Inhibition of the ERK protein by silibinin led to a significant decrease in mitochondrial membrane potential, which, in turn, caused Cytochrome C to be released from the mitochondria. The activation of downstream apoptotic pathways led to apoptosis of cholangiocarcinoma cells. In general, silibinin inhibited the growth of cholangiocarcinoma cell line xenograft tumors. Conclusions: Silibinin is able to inhibit cholangiocarcinoma through the ERK/mitochondrial apoptotic pathway, which makes silibinin a potential anti-tumor drug candidate for cholangiocarcinoma treatment. Frontiers Media S.A. 2022-03-23 /pmc/articles/PMC8983842/ /pubmed/35401195 http://dx.doi.org/10.3389/fphar.2022.847905 Text en Copyright © 2022 Bai, Chen, Hu, Wang, Wu and Yu. 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 Pharmacology
Bai, Yang
Chen, Jiaqi
Hu, Weijian
Wang, Lei
Wu, Yulian
Yu, Shi’an
Silibinin Therapy Improves Cholangiocarcinoma Outcomes by Regulating ERK/Mitochondrial Pathway
title Silibinin Therapy Improves Cholangiocarcinoma Outcomes by Regulating ERK/Mitochondrial Pathway
title_full Silibinin Therapy Improves Cholangiocarcinoma Outcomes by Regulating ERK/Mitochondrial Pathway
title_fullStr Silibinin Therapy Improves Cholangiocarcinoma Outcomes by Regulating ERK/Mitochondrial Pathway
title_full_unstemmed Silibinin Therapy Improves Cholangiocarcinoma Outcomes by Regulating ERK/Mitochondrial Pathway
title_short Silibinin Therapy Improves Cholangiocarcinoma Outcomes by Regulating ERK/Mitochondrial Pathway
title_sort silibinin therapy improves cholangiocarcinoma outcomes by regulating erk/mitochondrial pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983842/
https://www.ncbi.nlm.nih.gov/pubmed/35401195
http://dx.doi.org/10.3389/fphar.2022.847905
work_keys_str_mv AT baiyang silibinintherapyimprovescholangiocarcinomaoutcomesbyregulatingerkmitochondrialpathway
AT chenjiaqi silibinintherapyimprovescholangiocarcinomaoutcomesbyregulatingerkmitochondrialpathway
AT huweijian silibinintherapyimprovescholangiocarcinomaoutcomesbyregulatingerkmitochondrialpathway
AT wanglei silibinintherapyimprovescholangiocarcinomaoutcomesbyregulatingerkmitochondrialpathway
AT wuyulian silibinintherapyimprovescholangiocarcinomaoutcomesbyregulatingerkmitochondrialpathway
AT yushian silibinintherapyimprovescholangiocarcinomaoutcomesbyregulatingerkmitochondrialpathway