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Molecules 2013, 18(3), 2924-2933; doi:10.3390/molecules18032924

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

1
Department of Life Science, National Dong Hwa University, Hualien, 974, Taiwan
2
Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung 944, Taiwan
3
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
4
Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, Ain-Shams University, Organization of African Unity Street, Abassia, Cairo 11566, Egypt
5
National Museum of Marine Biology & Aquarium, Pingtung 944, Taiwan
6
Institute of Marine Biodiversity and Evolution, National Dong Hwa University, Pingtung 944, Taiwan
7
Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 831, Taiwan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 23 January 2013 / Revised: 22 February 2013 / Accepted: 25 February 2013 / Published: 4 March 2013
(This article belongs to the collection Bioactive Compounds)
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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.
Keywords: 5-episinuleptolide acetate; apoptosis; soft coral; Hsp90; mitochondria; ROS; Sinularia sp. 5-episinuleptolide acetate; apoptosis; soft coral; Hsp90; mitochondria; ROS; Sinularia sp.
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Huang, K.-J.; Chen, Y.-C.; El-Shazly, M.; Du, Y.-C.; Su, J.-H.; Tsao, C.-W.; Yen, W.-H.; Chang, W.-B.; Su, Y.-D.; Yeh, Y.-T.; Lu, M.-C. 5-Episinuleptolide Acetate, a Norcembranoidal Diterpene from the Formosan Soft Coral Sinularia sp., Induces Leukemia Cell Apoptosis through Hsp90 Inhibition. Molecules 2013, 18, 2924-2933.

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