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Thymoquinone suppresses migration of LoVo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation

AIM: To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration. METHODS: Our experiments used high dose thymoquinone (TQ) as an inhibitor to arrest LoVo (a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell prol...

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Autores principales: Hsu, Hsi-Hsien, Chen, Ming-Cheng, Day, Cecilia Hsuan, Lin, Yueh-Min, Li, Shin-Yi, Tu, Chuan-Chou, Padma, Viswanadha Vijaya, Shih, Hui-Nung, Kuo, Wei-Wen, Huang, Chih-Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323442/
https://www.ncbi.nlm.nih.gov/pubmed/28275297
http://dx.doi.org/10.3748/wjg.v23.i7.1171
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author Hsu, Hsi-Hsien
Chen, Ming-Cheng
Day, Cecilia Hsuan
Lin, Yueh-Min
Li, Shin-Yi
Tu, Chuan-Chou
Padma, Viswanadha Vijaya
Shih, Hui-Nung
Kuo, Wei-Wen
Huang, Chih-Yang
author_facet Hsu, Hsi-Hsien
Chen, Ming-Cheng
Day, Cecilia Hsuan
Lin, Yueh-Min
Li, Shin-Yi
Tu, Chuan-Chou
Padma, Viswanadha Vijaya
Shih, Hui-Nung
Kuo, Wei-Wen
Huang, Chih-Yang
author_sort Hsu, Hsi-Hsien
collection PubMed
description AIM: To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration. METHODS: Our experiments used high dose thymoquinone (TQ) as an inhibitor to arrest LoVo (a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell proliferation assay and immunoblotting assay. Low dose TQ did not significantly reduce LoVo cancer cell growth. Cyclooxygenase 2 (COX-2) is an enzyme that is involved in the conversion of arachidonic acid into prostaglandin E2 (PGE2) in humans. PGE2 can promote COX-2 protein expression and tumor cell proliferation and was used as a control. RESULTS: Our results showed that 20 μmol/L TQ significantly reduced human LoVo colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3K, p-Akt, p-GSK3β, and β-catenin and thereby inhibited the downstream COX-2 expression. Results also showed that the reduction in COX-2 expression resulted in a reduction in PGE2 levels and the suppression of EP2 and EP4 activation. Further analysis showed that TG treatment inhibited the nuclear translocation of β-catenin in LoVo cancer cells. The levels of the cofactors LEF-1 and TCF-4 were also decreased in the nucleus following TQ treatment in a dose-dependent manner. Treatment with low dose TQ inhibited the COX-2 expression at the transcriptional level and the regulation of COX-2 expression efficiently reduced LoVo cell migration. The results were further verified in vivo by confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice. CONCLUSION: TQ inhibits LoVo cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer.
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spelling pubmed-53234422017-03-08 Thymoquinone suppresses migration of LoVo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation Hsu, Hsi-Hsien Chen, Ming-Cheng Day, Cecilia Hsuan Lin, Yueh-Min Li, Shin-Yi Tu, Chuan-Chou Padma, Viswanadha Vijaya Shih, Hui-Nung Kuo, Wei-Wen Huang, Chih-Yang World J Gastroenterol Basic Study AIM: To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration. METHODS: Our experiments used high dose thymoquinone (TQ) as an inhibitor to arrest LoVo (a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell proliferation assay and immunoblotting assay. Low dose TQ did not significantly reduce LoVo cancer cell growth. Cyclooxygenase 2 (COX-2) is an enzyme that is involved in the conversion of arachidonic acid into prostaglandin E2 (PGE2) in humans. PGE2 can promote COX-2 protein expression and tumor cell proliferation and was used as a control. RESULTS: Our results showed that 20 μmol/L TQ significantly reduced human LoVo colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3K, p-Akt, p-GSK3β, and β-catenin and thereby inhibited the downstream COX-2 expression. Results also showed that the reduction in COX-2 expression resulted in a reduction in PGE2 levels and the suppression of EP2 and EP4 activation. Further analysis showed that TG treatment inhibited the nuclear translocation of β-catenin in LoVo cancer cells. The levels of the cofactors LEF-1 and TCF-4 were also decreased in the nucleus following TQ treatment in a dose-dependent manner. Treatment with low dose TQ inhibited the COX-2 expression at the transcriptional level and the regulation of COX-2 expression efficiently reduced LoVo cell migration. The results were further verified in vivo by confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice. CONCLUSION: TQ inhibits LoVo cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer. Baishideng Publishing Group Inc 2017-02-21 2017-02-21 /pmc/articles/PMC5323442/ /pubmed/28275297 http://dx.doi.org/10.3748/wjg.v23.i7.1171 Text en ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Basic Study
Hsu, Hsi-Hsien
Chen, Ming-Cheng
Day, Cecilia Hsuan
Lin, Yueh-Min
Li, Shin-Yi
Tu, Chuan-Chou
Padma, Viswanadha Vijaya
Shih, Hui-Nung
Kuo, Wei-Wen
Huang, Chih-Yang
Thymoquinone suppresses migration of LoVo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation
title Thymoquinone suppresses migration of LoVo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation
title_full Thymoquinone suppresses migration of LoVo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation
title_fullStr Thymoquinone suppresses migration of LoVo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation
title_full_unstemmed Thymoquinone suppresses migration of LoVo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation
title_short Thymoquinone suppresses migration of LoVo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation
title_sort thymoquinone suppresses migration of lovo human colon cancer cells by reducing prostaglandin e2 induced cox-2 activation
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323442/
https://www.ncbi.nlm.nih.gov/pubmed/28275297
http://dx.doi.org/10.3748/wjg.v23.i7.1171
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