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6,7-Dihydroxy-2-(4′-hydroxyphenyl)naphthalene induces HCT116 cell apoptosis through activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway
BACKGROUND: Colorectal cancer is the third leading cause of cancer-related deaths worldwide, and therefore, the development of novel drugs for its prevention and therapy are urgently required. This study aimed to determine the molecular mechanism of 6,7-dihydroxy-2-(4′-hydroxyphenyl) naphthalene (PN...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove Medical Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512798/ https://www.ncbi.nlm.nih.gov/pubmed/31190740 http://dx.doi.org/10.2147/DDDT.S193914 |
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author | Chiu, Ching-Feng Lai, Guan-Ying Chen, Chung-Hwan Chiu, Chien-Chao Hung, Shao-Wen Chang, Chi-Fen |
author_facet | Chiu, Ching-Feng Lai, Guan-Ying Chen, Chung-Hwan Chiu, Chien-Chao Hung, Shao-Wen Chang, Chi-Fen |
author_sort | Chiu, Ching-Feng |
collection | PubMed |
description | BACKGROUND: Colorectal cancer is the third leading cause of cancer-related deaths worldwide, and therefore, the development of novel drugs for its prevention and therapy are urgently required. This study aimed to determine the molecular mechanism of 6,7-dihydroxy-2-(4′-hydroxyphenyl) naphthalene (PNAP-6)-induced cytotoxicity in human colorectal cancer (HCT116) cells. METHODS: The effects of 2-phenylnaphthalene derivatives on HCT116 cell growth and viability were assessed by MTT assays. The mechanisms involved in the regulation of the extrinsic apoptosis and endoplasmic reticulum (ER) stress pathways by PNAP-6 were analyzed by annexin-V/propidium iodide flow cytometric analysis, Hoechst 33342 fluorescent staining, and Western blotting. RESULTS: PNAP-6 was shown to have an IC(50) value 15.20 μM. It induced G(2)/M phase arrest in HCT116 cells, associated with a marked decrease in cyclin B and CDK1 protein expression and increased caspase activation, PARP cleavage, chromatin condensation, and sub-G(1) apoptosis. Moreover, we found that the apoptotic effects of PNAP-6 proceeded through extrinsic apoptosis and ER stress pathways, by increasing the expression of Fas protein and ER stress markers, including PERK, ATF4, CHOP, p-IRE1α, and XBP-1s. CONCLUSION: These results suggest that 2-phenylnaphthalene derivatives, such as PNAP-6, have potential as new treatments for colorectal cancer. |
format | Online Article Text |
id | pubmed-6512798 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-65127982019-06-12 6,7-Dihydroxy-2-(4′-hydroxyphenyl)naphthalene induces HCT116 cell apoptosis through activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway Chiu, Ching-Feng Lai, Guan-Ying Chen, Chung-Hwan Chiu, Chien-Chao Hung, Shao-Wen Chang, Chi-Fen Drug Des Devel Ther Original Research BACKGROUND: Colorectal cancer is the third leading cause of cancer-related deaths worldwide, and therefore, the development of novel drugs for its prevention and therapy are urgently required. This study aimed to determine the molecular mechanism of 6,7-dihydroxy-2-(4′-hydroxyphenyl) naphthalene (PNAP-6)-induced cytotoxicity in human colorectal cancer (HCT116) cells. METHODS: The effects of 2-phenylnaphthalene derivatives on HCT116 cell growth and viability were assessed by MTT assays. The mechanisms involved in the regulation of the extrinsic apoptosis and endoplasmic reticulum (ER) stress pathways by PNAP-6 were analyzed by annexin-V/propidium iodide flow cytometric analysis, Hoechst 33342 fluorescent staining, and Western blotting. RESULTS: PNAP-6 was shown to have an IC(50) value 15.20 μM. It induced G(2)/M phase arrest in HCT116 cells, associated with a marked decrease in cyclin B and CDK1 protein expression and increased caspase activation, PARP cleavage, chromatin condensation, and sub-G(1) apoptosis. Moreover, we found that the apoptotic effects of PNAP-6 proceeded through extrinsic apoptosis and ER stress pathways, by increasing the expression of Fas protein and ER stress markers, including PERK, ATF4, CHOP, p-IRE1α, and XBP-1s. CONCLUSION: These results suggest that 2-phenylnaphthalene derivatives, such as PNAP-6, have potential as new treatments for colorectal cancer. Dove Medical Press 2019-05-09 /pmc/articles/PMC6512798/ /pubmed/31190740 http://dx.doi.org/10.2147/DDDT.S193914 Text en © 2019 Chiu et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Chiu, Ching-Feng Lai, Guan-Ying Chen, Chung-Hwan Chiu, Chien-Chao Hung, Shao-Wen Chang, Chi-Fen 6,7-Dihydroxy-2-(4′-hydroxyphenyl)naphthalene induces HCT116 cell apoptosis through activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway |
title | 6,7-Dihydroxy-2-(4′-hydroxyphenyl)naphthalene induces HCT116 cell apoptosis through activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway |
title_full | 6,7-Dihydroxy-2-(4′-hydroxyphenyl)naphthalene induces HCT116 cell apoptosis through activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway |
title_fullStr | 6,7-Dihydroxy-2-(4′-hydroxyphenyl)naphthalene induces HCT116 cell apoptosis through activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway |
title_full_unstemmed | 6,7-Dihydroxy-2-(4′-hydroxyphenyl)naphthalene induces HCT116 cell apoptosis through activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway |
title_short | 6,7-Dihydroxy-2-(4′-hydroxyphenyl)naphthalene induces HCT116 cell apoptosis through activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway |
title_sort | 6,7-dihydroxy-2-(4′-hydroxyphenyl)naphthalene induces hct116 cell apoptosis through activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512798/ https://www.ncbi.nlm.nih.gov/pubmed/31190740 http://dx.doi.org/10.2147/DDDT.S193914 |
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