Cargando…

A Garlic Derivative, S-allylcysteine (SAC), Suppresses Proliferation and Metastasis of Hepatocellular Carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is highly malignant and metastatic. Currently, there is no effective chemotherapy for patients with advanced HCC leading to an urgent need to seek for novel therapeutic options. We aimed to investigate the effect of a garlic derivative, S-allylcysteine (SAC...

Descripción completa

Detalles Bibliográficos
Autores principales: Ng, Kevin T. P., Guo, Dong Yong, Cheng, Qiao, Geng, Wei, Ling, Chang Chun, Li, Chang Xian, Liu, Xiao Bing, Ma, Yuen Yuen, Lo, Chung Mau, Poon, Ronnie T. P., Fan, Sheung Tat, Man, Kwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3289621/
https://www.ncbi.nlm.nih.gov/pubmed/22389672
http://dx.doi.org/10.1371/journal.pone.0031655
_version_ 1782224883545014272
author Ng, Kevin T. P.
Guo, Dong Yong
Cheng, Qiao
Geng, Wei
Ling, Chang Chun
Li, Chang Xian
Liu, Xiao Bing
Ma, Yuen Yuen
Lo, Chung Mau
Poon, Ronnie T. P.
Fan, Sheung Tat
Man, Kwan
author_facet Ng, Kevin T. P.
Guo, Dong Yong
Cheng, Qiao
Geng, Wei
Ling, Chang Chun
Li, Chang Xian
Liu, Xiao Bing
Ma, Yuen Yuen
Lo, Chung Mau
Poon, Ronnie T. P.
Fan, Sheung Tat
Man, Kwan
author_sort Ng, Kevin T. P.
collection PubMed
description BACKGROUND: Hepatocellular carcinoma (HCC) is highly malignant and metastatic. Currently, there is no effective chemotherapy for patients with advanced HCC leading to an urgent need to seek for novel therapeutic options. We aimed to investigate the effect of a garlic derivative, S-allylcysteine (SAC), on the proliferation and metastasis of HCC. METHODOLOGY/PRINCIPAL FINDINGS: A series of in vitro experiments including MTT, colony-forming, wound-healing, invasion, apoptosis and cell cycle assays were performed to examine the anti-proliferative and anti-metastatic effects of SAC on a metastatic HCC cell line MHCC97L. The therapeutic values of SAC single and combined with cisplatin treatments were examined in an in vivo orthotopic xenograft liver tumor model. The result showed that the proliferation rate and colony-forming abilities of MHCC97L cells were suppressed by SAC together with significant suppression of the expressions of proliferation markers, Ki-67 and proliferating cell nuclear antigen (PCNA). Moreover, SAC hindered the migration and invasion of MHCC97L cells corresponding with up-regulation of E-cadherin and down-regulation of VEGF. Furthermore, SAC significantly induced apoptosis and necrosis of MHCC97L cells through suppressing Bcl-xL and Bcl-2 as well as activating caspase-3 and caspase-9. In addition, SAC could significantly induce the S phase arrest of MHCC97L cells together with down-regulation of cdc25c, cdc2 and cyclin B1. In vivo xenograft liver tumor model demonstrated that SAC single or combined with cisplatin treatment inhibited the progression and metastasis of HCC tumor. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the anti-proliferative and anti-metastatic effects of SAC on HCC cells and suggest that SAC may be a potential therapeutic agent for the treatment of HCC patients.
format Online
Article
Text
id pubmed-3289621
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-32896212012-03-02 A Garlic Derivative, S-allylcysteine (SAC), Suppresses Proliferation and Metastasis of Hepatocellular Carcinoma Ng, Kevin T. P. Guo, Dong Yong Cheng, Qiao Geng, Wei Ling, Chang Chun Li, Chang Xian Liu, Xiao Bing Ma, Yuen Yuen Lo, Chung Mau Poon, Ronnie T. P. Fan, Sheung Tat Man, Kwan PLoS One Research Article BACKGROUND: Hepatocellular carcinoma (HCC) is highly malignant and metastatic. Currently, there is no effective chemotherapy for patients with advanced HCC leading to an urgent need to seek for novel therapeutic options. We aimed to investigate the effect of a garlic derivative, S-allylcysteine (SAC), on the proliferation and metastasis of HCC. METHODOLOGY/PRINCIPAL FINDINGS: A series of in vitro experiments including MTT, colony-forming, wound-healing, invasion, apoptosis and cell cycle assays were performed to examine the anti-proliferative and anti-metastatic effects of SAC on a metastatic HCC cell line MHCC97L. The therapeutic values of SAC single and combined with cisplatin treatments were examined in an in vivo orthotopic xenograft liver tumor model. The result showed that the proliferation rate and colony-forming abilities of MHCC97L cells were suppressed by SAC together with significant suppression of the expressions of proliferation markers, Ki-67 and proliferating cell nuclear antigen (PCNA). Moreover, SAC hindered the migration and invasion of MHCC97L cells corresponding with up-regulation of E-cadherin and down-regulation of VEGF. Furthermore, SAC significantly induced apoptosis and necrosis of MHCC97L cells through suppressing Bcl-xL and Bcl-2 as well as activating caspase-3 and caspase-9. In addition, SAC could significantly induce the S phase arrest of MHCC97L cells together with down-regulation of cdc25c, cdc2 and cyclin B1. In vivo xenograft liver tumor model demonstrated that SAC single or combined with cisplatin treatment inhibited the progression and metastasis of HCC tumor. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the anti-proliferative and anti-metastatic effects of SAC on HCC cells and suggest that SAC may be a potential therapeutic agent for the treatment of HCC patients. Public Library of Science 2012-02-28 /pmc/articles/PMC3289621/ /pubmed/22389672 http://dx.doi.org/10.1371/journal.pone.0031655 Text en Ng et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ng, Kevin T. P.
Guo, Dong Yong
Cheng, Qiao
Geng, Wei
Ling, Chang Chun
Li, Chang Xian
Liu, Xiao Bing
Ma, Yuen Yuen
Lo, Chung Mau
Poon, Ronnie T. P.
Fan, Sheung Tat
Man, Kwan
A Garlic Derivative, S-allylcysteine (SAC), Suppresses Proliferation and Metastasis of Hepatocellular Carcinoma
title A Garlic Derivative, S-allylcysteine (SAC), Suppresses Proliferation and Metastasis of Hepatocellular Carcinoma
title_full A Garlic Derivative, S-allylcysteine (SAC), Suppresses Proliferation and Metastasis of Hepatocellular Carcinoma
title_fullStr A Garlic Derivative, S-allylcysteine (SAC), Suppresses Proliferation and Metastasis of Hepatocellular Carcinoma
title_full_unstemmed A Garlic Derivative, S-allylcysteine (SAC), Suppresses Proliferation and Metastasis of Hepatocellular Carcinoma
title_short A Garlic Derivative, S-allylcysteine (SAC), Suppresses Proliferation and Metastasis of Hepatocellular Carcinoma
title_sort garlic derivative, s-allylcysteine (sac), suppresses proliferation and metastasis of hepatocellular carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3289621/
https://www.ncbi.nlm.nih.gov/pubmed/22389672
http://dx.doi.org/10.1371/journal.pone.0031655
work_keys_str_mv AT ngkevintp agarlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT guodongyong agarlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT chengqiao agarlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT gengwei agarlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT lingchangchun agarlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT lichangxian agarlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT liuxiaobing agarlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT mayuenyuen agarlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT lochungmau agarlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT poonronnietp agarlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT fansheungtat agarlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT mankwan agarlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT ngkevintp garlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT guodongyong garlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT chengqiao garlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT gengwei garlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT lingchangchun garlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT lichangxian garlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT liuxiaobing garlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT mayuenyuen garlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT lochungmau garlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT poonronnietp garlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT fansheungtat garlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma
AT mankwan garlicderivativesallylcysteinesacsuppressesproliferationandmetastasisofhepatocellularcarcinoma