Cargando…

Hinokitiol Inhibits Migration of A549 Lung Cancer Cells via Suppression of MMPs and Induction of Antioxidant Enzymes and Apoptosis

Hinokitiol, a natural monoterpenoid from the heartwood of Calocedrus formosana, has been reported to have anticancer effects against various cancer cell lines. However, the detailed molecular mechanisms and the inhibiting roles of hinokitiol on adenocarcinoma A549 cells remain to be fully elucidated...

Descripción completa

Detalles Bibliográficos
Autores principales: Jayakumar, Thanasekaran, Liu, Chao-Hong, Wu, Guan-Yi, Lee, Tzu-Yin, Manubolu, Manjunath, Hsieh, Cheng-Ying, Yang, Chih-Hao, Sheu, Joen-Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979393/
https://www.ncbi.nlm.nih.gov/pubmed/29565268
http://dx.doi.org/10.3390/ijms19040939
_version_ 1783327685580161024
author Jayakumar, Thanasekaran
Liu, Chao-Hong
Wu, Guan-Yi
Lee, Tzu-Yin
Manubolu, Manjunath
Hsieh, Cheng-Ying
Yang, Chih-Hao
Sheu, Joen-Rong
author_facet Jayakumar, Thanasekaran
Liu, Chao-Hong
Wu, Guan-Yi
Lee, Tzu-Yin
Manubolu, Manjunath
Hsieh, Cheng-Ying
Yang, Chih-Hao
Sheu, Joen-Rong
author_sort Jayakumar, Thanasekaran
collection PubMed
description Hinokitiol, a natural monoterpenoid from the heartwood of Calocedrus formosana, has been reported to have anticancer effects against various cancer cell lines. However, the detailed molecular mechanisms and the inhibiting roles of hinokitiol on adenocarcinoma A549 cells remain to be fully elucidated. Thus, the current study was designed to evaluate the effect of hinokitiol on the migration of human lung adenocarcinoma A549 cells in vitro. The data demonstrates that hinokitiol does not effectively inhibit the viability of A549 cells at up to a 10 µM concentration. When treated with non-toxic doses (1–5 µM) of hinokitiol, the cell migration is markedly suppressed at 5 µM. Hinokitiol significantly reduced p53 expression, followed by attenuation of Bax in A549 cells. A dose-dependent inhibition of activated caspase-9 and -3 was observed in the presence of hinokitiol. An observed increase in protein expression of matrix metalloproteinases (MMPs) -2/-9 in A549 cells was significantly inhibited by hinokitiol. Remarkably, when A549 cells were subjected to hinokitiol (1–5 µM), there was an increase in the activities of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) from the reduction in cells. In addition, the incubation of A549 cells with hinokitiol significantly activated the cytochrome c expression, which may be triggered by activation of caspase-9 followed by caspase-3. These observations indicate that hinokitiol inhibited the migration of lung cancer A549 cells through several mechanisms, including the activation of caspases-9 and -3, induction of p53/Bax and antioxidant CAT and SOD, and reduction of MMP-2 and -9 activities. It also induces cytochrome c expression. These findings demonstrate a new therapeutic potential for hinokitiol in lung cancer chemoprevention.
format Online
Article
Text
id pubmed-5979393
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-59793932018-06-10 Hinokitiol Inhibits Migration of A549 Lung Cancer Cells via Suppression of MMPs and Induction of Antioxidant Enzymes and Apoptosis Jayakumar, Thanasekaran Liu, Chao-Hong Wu, Guan-Yi Lee, Tzu-Yin Manubolu, Manjunath Hsieh, Cheng-Ying Yang, Chih-Hao Sheu, Joen-Rong Int J Mol Sci Article Hinokitiol, a natural monoterpenoid from the heartwood of Calocedrus formosana, has been reported to have anticancer effects against various cancer cell lines. However, the detailed molecular mechanisms and the inhibiting roles of hinokitiol on adenocarcinoma A549 cells remain to be fully elucidated. Thus, the current study was designed to evaluate the effect of hinokitiol on the migration of human lung adenocarcinoma A549 cells in vitro. The data demonstrates that hinokitiol does not effectively inhibit the viability of A549 cells at up to a 10 µM concentration. When treated with non-toxic doses (1–5 µM) of hinokitiol, the cell migration is markedly suppressed at 5 µM. Hinokitiol significantly reduced p53 expression, followed by attenuation of Bax in A549 cells. A dose-dependent inhibition of activated caspase-9 and -3 was observed in the presence of hinokitiol. An observed increase in protein expression of matrix metalloproteinases (MMPs) -2/-9 in A549 cells was significantly inhibited by hinokitiol. Remarkably, when A549 cells were subjected to hinokitiol (1–5 µM), there was an increase in the activities of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) from the reduction in cells. In addition, the incubation of A549 cells with hinokitiol significantly activated the cytochrome c expression, which may be triggered by activation of caspase-9 followed by caspase-3. These observations indicate that hinokitiol inhibited the migration of lung cancer A549 cells through several mechanisms, including the activation of caspases-9 and -3, induction of p53/Bax and antioxidant CAT and SOD, and reduction of MMP-2 and -9 activities. It also induces cytochrome c expression. These findings demonstrate a new therapeutic potential for hinokitiol in lung cancer chemoprevention. MDPI 2018-03-22 /pmc/articles/PMC5979393/ /pubmed/29565268 http://dx.doi.org/10.3390/ijms19040939 Text en © 2018 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
Jayakumar, Thanasekaran
Liu, Chao-Hong
Wu, Guan-Yi
Lee, Tzu-Yin
Manubolu, Manjunath
Hsieh, Cheng-Ying
Yang, Chih-Hao
Sheu, Joen-Rong
Hinokitiol Inhibits Migration of A549 Lung Cancer Cells via Suppression of MMPs and Induction of Antioxidant Enzymes and Apoptosis
title Hinokitiol Inhibits Migration of A549 Lung Cancer Cells via Suppression of MMPs and Induction of Antioxidant Enzymes and Apoptosis
title_full Hinokitiol Inhibits Migration of A549 Lung Cancer Cells via Suppression of MMPs and Induction of Antioxidant Enzymes and Apoptosis
title_fullStr Hinokitiol Inhibits Migration of A549 Lung Cancer Cells via Suppression of MMPs and Induction of Antioxidant Enzymes and Apoptosis
title_full_unstemmed Hinokitiol Inhibits Migration of A549 Lung Cancer Cells via Suppression of MMPs and Induction of Antioxidant Enzymes and Apoptosis
title_short Hinokitiol Inhibits Migration of A549 Lung Cancer Cells via Suppression of MMPs and Induction of Antioxidant Enzymes and Apoptosis
title_sort hinokitiol inhibits migration of a549 lung cancer cells via suppression of mmps and induction of antioxidant enzymes and apoptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979393/
https://www.ncbi.nlm.nih.gov/pubmed/29565268
http://dx.doi.org/10.3390/ijms19040939
work_keys_str_mv AT jayakumarthanasekaran hinokitiolinhibitsmigrationofa549lungcancercellsviasuppressionofmmpsandinductionofantioxidantenzymesandapoptosis
AT liuchaohong hinokitiolinhibitsmigrationofa549lungcancercellsviasuppressionofmmpsandinductionofantioxidantenzymesandapoptosis
AT wuguanyi hinokitiolinhibitsmigrationofa549lungcancercellsviasuppressionofmmpsandinductionofantioxidantenzymesandapoptosis
AT leetzuyin hinokitiolinhibitsmigrationofa549lungcancercellsviasuppressionofmmpsandinductionofantioxidantenzymesandapoptosis
AT manubolumanjunath hinokitiolinhibitsmigrationofa549lungcancercellsviasuppressionofmmpsandinductionofantioxidantenzymesandapoptosis
AT hsiehchengying hinokitiolinhibitsmigrationofa549lungcancercellsviasuppressionofmmpsandinductionofantioxidantenzymesandapoptosis
AT yangchihhao hinokitiolinhibitsmigrationofa549lungcancercellsviasuppressionofmmpsandinductionofantioxidantenzymesandapoptosis
AT sheujoenrong hinokitiolinhibitsmigrationofa549lungcancercellsviasuppressionofmmpsandinductionofantioxidantenzymesandapoptosis