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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
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.
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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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