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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Published inMolecules (Basel, Switzerland) Vol. 18; no. 3; pp. 2924 - 2933
Main Authors 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
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 04.03.2013
MDPI
Subjects
5-episinuleptolide acetate
Animals
Anthozoa - chemistry
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Cancer
Cell Line, Tumor
Cell Proliferation - drug effects
Cells
Cytotoxicity
Diterpenes - chemistry
Diterpenes - pharmacology
Dose-Response Relationship, Drug
HL-60 Cells
Hsp90
HSP90 Heat-Shock Proteins - antagonists & inhibitors
Humans
K562 Cells
Leukemia
Leukemia - metabolism
mitochondria
Mitochondria - drug effects
Mitochondria - metabolism
Natural products
Pharmacy
Proteins
ROS
Signal transduction
Sinularia sp
soft coral
Taiwan
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Summary: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.
Bibliography:These authors contributed equally to this work.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules18032924