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

Molecules

Kao-Jean Huang¹  Yu-Cheng Chen³  Mohamed El-Shazly²  Ying-Chi Du²  Jui-Hsin Su³  Chia-Wei Tsao³  Wei-Hsuan Yen³  Wen-Been Chang⁵  Yin-Di Su³  Yao-Tsung Yeh⁴ 

[1] Department of Life Science, National Dong Hwa University, Hualien, 974, Taiwan;Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan;Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung 944, Taiwan;Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 831, Taiwan;National Museum of Marine Biology & Aquarium, Pingtung 944, Taiwan

关键词: 5-episinuleptolide acetate;    apoptosis;    soft coral;    Hsp90;    mitochondria;    ROS;    Sinularia sp.;   

DOI  :  10.3390/molecules18032924

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2013 by the authors; licensee MDPI, Basel, Switzerland.