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5-Episinuleptolide Acetate, a Norcembranoidal Diterpene from the Formosan Soft Coral Sinularia sp., Induces Leukemia Cell Apoptosis through Hsp90 Inhibition

Authors :
Yao-Tsung Yeh
Wen-Been Chang
Yin-Di Su
Wei-Hsuan Yen
Chia-Wei Tsao
Jui-Hsin Su
Ying-Chi Du
Mohamed El-Shazly
Kao-Jean Huang
Yu-Cheng Chen
Mei-Chin Lu
Source :
Molecules, Vol 18, Iss 3, Pp 2924-2933 (2013)
Publication Year :
2013
Publisher :
MDPI AG, 2013.

Abstract

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.

Details

Language :
English
ISSN :
14203049
Volume :
18
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.370f18a9fc8456ca44713f1a3101e8a
Document Type :
article
Full Text :
https://doi.org/10.3390/molecules18032924