Cargando…

Xanthones from the Bark of Garcinia xanthochymus and the Mechanism of Induced Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells via the Mitochondrial Pathway

Xanthones are important chemical constituents of Garcinia xanthochymus and varied bioactivities including cytotoxicity. However, their anti-tumor mechanism has remained unknown. Here, we isolated and identified a new xanthone named garciniaxanthone I (1) and five known compounds from the bark of G....

Descripción completa

Detalles Bibliográficos
Autores principales: Jin, Shan, Shi, Kuan, Liu, Liu, Chen, Yu, Yang, Guangzhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801373/
https://www.ncbi.nlm.nih.gov/pubmed/31569691
http://dx.doi.org/10.3390/ijms20194803
_version_ 1783460556720570368
author Jin, Shan
Shi, Kuan
Liu, Liu
Chen, Yu
Yang, Guangzhong
author_facet Jin, Shan
Shi, Kuan
Liu, Liu
Chen, Yu
Yang, Guangzhong
author_sort Jin, Shan
collection PubMed
description Xanthones are important chemical constituents of Garcinia xanthochymus and varied bioactivities including cytotoxicity. However, their anti-tumor mechanism has remained unknown. Here, we isolated and identified a new xanthone named garciniaxanthone I (1) and five known compounds from the bark of G. xanthochymus. Their structures were elucidated by NMR analysis and HRESIMS. The anti-proliferation activities of all isolated compounds were evaluated on four human tumor cell lines (HepG2, A549, SGC7901, MCF-7). The results demonstrated that the anti-proliferation activity of xanthone was related to the number and location of prenyl groups. We further found that garciniaxanthone I (GXI) could induce HepG2 apoptosis and enhance the expression of cleaved caspase-8, caspase-9, and caspase-3. GXI could also increase Bax level and concurrently reduce the overexpression of Bcl-2, Bcl-XL, Mcl-1, and surviving in HepG2 cells. Moreover, GXI could inhibit cell migration of HepG2 cells by inhibiting the expressions of MMP-7 and MMP-9. In summary, our study suggests that GXI could induce HepG2 apoptosis via the mitochondrial pathway and might become a lead compound for liver cancer treatment.
format Online
Article
Text
id pubmed-6801373
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-68013732019-10-31 Xanthones from the Bark of Garcinia xanthochymus and the Mechanism of Induced Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells via the Mitochondrial Pathway Jin, Shan Shi, Kuan Liu, Liu Chen, Yu Yang, Guangzhong Int J Mol Sci Article Xanthones are important chemical constituents of Garcinia xanthochymus and varied bioactivities including cytotoxicity. However, their anti-tumor mechanism has remained unknown. Here, we isolated and identified a new xanthone named garciniaxanthone I (1) and five known compounds from the bark of G. xanthochymus. Their structures were elucidated by NMR analysis and HRESIMS. The anti-proliferation activities of all isolated compounds were evaluated on four human tumor cell lines (HepG2, A549, SGC7901, MCF-7). The results demonstrated that the anti-proliferation activity of xanthone was related to the number and location of prenyl groups. We further found that garciniaxanthone I (GXI) could induce HepG2 apoptosis and enhance the expression of cleaved caspase-8, caspase-9, and caspase-3. GXI could also increase Bax level and concurrently reduce the overexpression of Bcl-2, Bcl-XL, Mcl-1, and surviving in HepG2 cells. Moreover, GXI could inhibit cell migration of HepG2 cells by inhibiting the expressions of MMP-7 and MMP-9. In summary, our study suggests that GXI could induce HepG2 apoptosis via the mitochondrial pathway and might become a lead compound for liver cancer treatment. MDPI 2019-09-27 /pmc/articles/PMC6801373/ /pubmed/31569691 http://dx.doi.org/10.3390/ijms20194803 Text en © 2019 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
Jin, Shan
Shi, Kuan
Liu, Liu
Chen, Yu
Yang, Guangzhong
Xanthones from the Bark of Garcinia xanthochymus and the Mechanism of Induced Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells via the Mitochondrial Pathway
title Xanthones from the Bark of Garcinia xanthochymus and the Mechanism of Induced Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells via the Mitochondrial Pathway
title_full Xanthones from the Bark of Garcinia xanthochymus and the Mechanism of Induced Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells via the Mitochondrial Pathway
title_fullStr Xanthones from the Bark of Garcinia xanthochymus and the Mechanism of Induced Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells via the Mitochondrial Pathway
title_full_unstemmed Xanthones from the Bark of Garcinia xanthochymus and the Mechanism of Induced Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells via the Mitochondrial Pathway
title_short Xanthones from the Bark of Garcinia xanthochymus and the Mechanism of Induced Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells via the Mitochondrial Pathway
title_sort xanthones from the bark of garcinia xanthochymus and the mechanism of induced apoptosis in human hepatocellular carcinoma hepg2 cells via the mitochondrial pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801373/
https://www.ncbi.nlm.nih.gov/pubmed/31569691
http://dx.doi.org/10.3390/ijms20194803
work_keys_str_mv AT jinshan xanthonesfromthebarkofgarciniaxanthochymusandthemechanismofinducedapoptosisinhumanhepatocellularcarcinomahepg2cellsviathemitochondrialpathway
AT shikuan xanthonesfromthebarkofgarciniaxanthochymusandthemechanismofinducedapoptosisinhumanhepatocellularcarcinomahepg2cellsviathemitochondrialpathway
AT liuliu xanthonesfromthebarkofgarciniaxanthochymusandthemechanismofinducedapoptosisinhumanhepatocellularcarcinomahepg2cellsviathemitochondrialpathway
AT chenyu xanthonesfromthebarkofgarciniaxanthochymusandthemechanismofinducedapoptosisinhumanhepatocellularcarcinomahepg2cellsviathemitochondrialpathway
AT yangguangzhong xanthonesfromthebarkofgarciniaxanthochymusandthemechanismofinducedapoptosisinhumanhepatocellularcarcinomahepg2cellsviathemitochondrialpathway