Cargando…

Apoptotic Effects of Xanthium strumarium via PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma

Xanthium strumarium (XS) has been traditionally used as a medicinal herb for treating inflammatory diseases, such as appendicitis, chronic bronchitis, rheumatism, and rhinitis. In this study, we yielded ethanol extracts from XS and investigated whether they could inhibit the progression of hepatocel...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Juyoung, Jung, Kyung Hee, Ryu, Hyung Won, Kim, Doo-Young, Oh, Sei-Ryang, Hong, Soon-Sun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925706/
https://www.ncbi.nlm.nih.gov/pubmed/31885640
http://dx.doi.org/10.1155/2019/2176701
_version_ 1783481956273487872
author Kim, Juyoung
Jung, Kyung Hee
Ryu, Hyung Won
Kim, Doo-Young
Oh, Sei-Ryang
Hong, Soon-Sun
author_facet Kim, Juyoung
Jung, Kyung Hee
Ryu, Hyung Won
Kim, Doo-Young
Oh, Sei-Ryang
Hong, Soon-Sun
author_sort Kim, Juyoung
collection PubMed
description Xanthium strumarium (XS) has been traditionally used as a medicinal herb for treating inflammatory diseases, such as appendicitis, chronic bronchitis, rheumatism, and rhinitis. In this study, we yielded ethanol extracts from XS and investigated whether they could inhibit the progression of hepatocellular carcinoma (HCC) and its underlying mechanism. The XS-5 and XS-6 extracts dose-dependently inhibited the growth and proliferation in HCC cell lines. The apoptotic effects of them were observed via increased levels of cleaved caspase-3 and cleaved PARP, as well as elevated numbers of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling- (TUNEL-) positive apoptotic cells. They also decreased XIAP and Mcl-1 expression via loss of mitochondrial membrane potential. Additionally, they inhibited the invasion and migration of HCC cells. In an ex vivo model, the extracts significantly inhibited tumor cell growth and induced apoptosis by increasing the expression of the cleaved caspase-3. A mechanistic study revealed that they effectively suppressed PI3K/AKT/mTOR signaling pathways in HCC cells. Taken together, our findings demonstrate that they could efficiently not only induce apoptosis but also inhibit cell growth, migration, and invasion of human HCC cells by blocking the PI3K/AKT/mTOR pathway. We suggest XS-5 and XS-6 as novel natural anti-HCC agents.
format Online
Article
Text
id pubmed-6925706
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-69257062019-12-29 Apoptotic Effects of Xanthium strumarium via PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma Kim, Juyoung Jung, Kyung Hee Ryu, Hyung Won Kim, Doo-Young Oh, Sei-Ryang Hong, Soon-Sun Evid Based Complement Alternat Med Research Article Xanthium strumarium (XS) has been traditionally used as a medicinal herb for treating inflammatory diseases, such as appendicitis, chronic bronchitis, rheumatism, and rhinitis. In this study, we yielded ethanol extracts from XS and investigated whether they could inhibit the progression of hepatocellular carcinoma (HCC) and its underlying mechanism. The XS-5 and XS-6 extracts dose-dependently inhibited the growth and proliferation in HCC cell lines. The apoptotic effects of them were observed via increased levels of cleaved caspase-3 and cleaved PARP, as well as elevated numbers of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling- (TUNEL-) positive apoptotic cells. They also decreased XIAP and Mcl-1 expression via loss of mitochondrial membrane potential. Additionally, they inhibited the invasion and migration of HCC cells. In an ex vivo model, the extracts significantly inhibited tumor cell growth and induced apoptosis by increasing the expression of the cleaved caspase-3. A mechanistic study revealed that they effectively suppressed PI3K/AKT/mTOR signaling pathways in HCC cells. Taken together, our findings demonstrate that they could efficiently not only induce apoptosis but also inhibit cell growth, migration, and invasion of human HCC cells by blocking the PI3K/AKT/mTOR pathway. We suggest XS-5 and XS-6 as novel natural anti-HCC agents. Hindawi 2019-11-07 /pmc/articles/PMC6925706/ /pubmed/31885640 http://dx.doi.org/10.1155/2019/2176701 Text en Copyright © 2019 Juyoung Kim et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kim, Juyoung
Jung, Kyung Hee
Ryu, Hyung Won
Kim, Doo-Young
Oh, Sei-Ryang
Hong, Soon-Sun
Apoptotic Effects of Xanthium strumarium via PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma
title Apoptotic Effects of Xanthium strumarium via PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma
title_full Apoptotic Effects of Xanthium strumarium via PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma
title_fullStr Apoptotic Effects of Xanthium strumarium via PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma
title_full_unstemmed Apoptotic Effects of Xanthium strumarium via PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma
title_short Apoptotic Effects of Xanthium strumarium via PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma
title_sort apoptotic effects of xanthium strumarium via pi3k/akt/mtor pathway in hepatocellular carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925706/
https://www.ncbi.nlm.nih.gov/pubmed/31885640
http://dx.doi.org/10.1155/2019/2176701
work_keys_str_mv AT kimjuyoung apoptoticeffectsofxanthiumstrumariumviapi3kaktmtorpathwayinhepatocellularcarcinoma
AT jungkyunghee apoptoticeffectsofxanthiumstrumariumviapi3kaktmtorpathwayinhepatocellularcarcinoma
AT ryuhyungwon apoptoticeffectsofxanthiumstrumariumviapi3kaktmtorpathwayinhepatocellularcarcinoma
AT kimdooyoung apoptoticeffectsofxanthiumstrumariumviapi3kaktmtorpathwayinhepatocellularcarcinoma
AT ohseiryang apoptoticeffectsofxanthiumstrumariumviapi3kaktmtorpathwayinhepatocellularcarcinoma
AT hongsoonsun apoptoticeffectsofxanthiumstrumariumviapi3kaktmtorpathwayinhepatocellularcarcinoma