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5-Episinuleptolide Acetate, a Norcembranoidal Diterpene from the Formosan Soft Coral Sinularia sp., Induces Leukemia Cell Apoptosis through Hsp90 Inhibition
5-Episinuleptolide acetate (5EPA), a cytotoxic norcembranoidal diterpene recently identified from the Formosan soft coral Sinularia sp., exhibited potent activity against the K562, Molt 4 and HL 60 cancer cell lines. The antiproliferative assay, as well as the annexin V-FITC/propidium iodide (PI) ap...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270000/ https://www.ncbi.nlm.nih.gov/pubmed/23459302 http://dx.doi.org/10.3390/molecules18032924 |
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author | Huang, Kao-Jean Chen, Yu-Cheng El-Shazly, Mohamed Du, Ying-Chi Su, Jui-Hsin Tsao, Chia-Wei Yen, Wei-Hsuan Chang, Wen-Been Su, Yin-Di Yeh, Yao-Tsung Lu, Mei-Chin |
author_facet | Huang, Kao-Jean Chen, Yu-Cheng El-Shazly, Mohamed Du, Ying-Chi Su, Jui-Hsin Tsao, Chia-Wei Yen, Wei-Hsuan Chang, Wen-Been Su, Yin-Di Yeh, Yao-Tsung Lu, Mei-Chin |
author_sort | Huang, Kao-Jean |
collection | PubMed |
description | 5-Episinuleptolide acetate (5EPA), a cytotoxic norcembranoidal diterpene recently identified from the Formosan soft coral Sinularia sp., exhibited potent activity against the K562, Molt 4 and HL 60 cancer cell lines. The antiproliferative assay, as well as the annexin V-FITC/propidium iodide (PI) apoptotic assay, indicated that the HL 60 cell line is the most sensitive one towards 5EPA. This diterpenoid led to caspases -3, -8, and -9 activation as well as PARP cleavage. It also induced ROS generation, calcium accumulation and disruption of mitochondrial membrane potential. Additionally, the expression levels of Hsp90 protein and several client proteins were downregulated in response to 5EPA treatment. These results suggest that 5EPA’s cytotoxic effect on HL 60 cells may be attributed to the inhibition of Hsp90 as well as the induction of mitochondrial stress which finally results in apoptotic cell death. |
format | Online Article Text |
id | pubmed-6270000 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62700002018-12-20 5-Episinuleptolide Acetate, a Norcembranoidal Diterpene from the Formosan Soft Coral Sinularia sp., Induces Leukemia Cell Apoptosis through Hsp90 Inhibition Huang, Kao-Jean Chen, Yu-Cheng El-Shazly, Mohamed Du, Ying-Chi Su, Jui-Hsin Tsao, Chia-Wei Yen, Wei-Hsuan Chang, Wen-Been Su, Yin-Di Yeh, Yao-Tsung Lu, Mei-Chin Molecules Article 5-Episinuleptolide acetate (5EPA), a cytotoxic norcembranoidal diterpene recently identified from the Formosan soft coral Sinularia sp., exhibited potent activity against the K562, Molt 4 and HL 60 cancer cell lines. The antiproliferative assay, as well as the annexin V-FITC/propidium iodide (PI) apoptotic assay, indicated that the HL 60 cell line is the most sensitive one towards 5EPA. This diterpenoid led to caspases -3, -8, and -9 activation as well as PARP cleavage. It also induced ROS generation, calcium accumulation and disruption of mitochondrial membrane potential. Additionally, the expression levels of Hsp90 protein and several client proteins were downregulated in response to 5EPA treatment. These results suggest that 5EPA’s cytotoxic effect on HL 60 cells may be attributed to the inhibition of Hsp90 as well as the induction of mitochondrial stress which finally results in apoptotic cell death. MDPI 2013-03-04 /pmc/articles/PMC6270000/ /pubmed/23459302 http://dx.doi.org/10.3390/molecules18032924 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Huang, Kao-Jean Chen, Yu-Cheng El-Shazly, Mohamed Du, Ying-Chi Su, Jui-Hsin Tsao, Chia-Wei Yen, Wei-Hsuan Chang, Wen-Been Su, Yin-Di Yeh, Yao-Tsung Lu, Mei-Chin 5-Episinuleptolide Acetate, a Norcembranoidal Diterpene from the Formosan Soft Coral Sinularia sp., Induces Leukemia Cell Apoptosis through Hsp90 Inhibition |
title | 5-Episinuleptolide Acetate, a Norcembranoidal Diterpene from the Formosan Soft Coral Sinularia sp., Induces Leukemia Cell Apoptosis through Hsp90 Inhibition |
title_full | 5-Episinuleptolide Acetate, a Norcembranoidal Diterpene from the Formosan Soft Coral Sinularia sp., Induces Leukemia Cell Apoptosis through Hsp90 Inhibition |
title_fullStr | 5-Episinuleptolide Acetate, a Norcembranoidal Diterpene from the Formosan Soft Coral Sinularia sp., Induces Leukemia Cell Apoptosis through Hsp90 Inhibition |
title_full_unstemmed | 5-Episinuleptolide Acetate, a Norcembranoidal Diterpene from the Formosan Soft Coral Sinularia sp., Induces Leukemia Cell Apoptosis through Hsp90 Inhibition |
title_short | 5-Episinuleptolide Acetate, a Norcembranoidal Diterpene from the Formosan Soft Coral Sinularia sp., Induces Leukemia Cell Apoptosis through Hsp90 Inhibition |
title_sort | 5-episinuleptolide acetate, a norcembranoidal diterpene from the formosan soft coral sinularia sp., induces leukemia cell apoptosis through hsp90 inhibition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270000/ https://www.ncbi.nlm.nih.gov/pubmed/23459302 http://dx.doi.org/10.3390/molecules18032924 |
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