5-Episinuleptolide acetate, a norcembranoidal diterpene from the formosan soft coral Sinularia sp., induces leukemia cell apoptosis through Hsp90 inhibition.

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.

• Authors: Kao-Jean Huang, Yu-Cheng Chen, Mohamed El-Shazly, Ying-Chi Du, Jui-Hsin Su, Chia-Wei Tsao, Wei-Hsuan Yen, Wen-Been Chang, Yin-Di Su, Yao-Tsung Yeh, Mei-Chin Lu
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 18 Issue 3 Pg. 2924-33 (Mar 04 2013) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 23459302 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5-episinuleptolide
• Antineoplastic Agents
• Diterpenes
• HSP90 Heat-Shock Proteins

Topics

• Animals
• Anthozoa (chemistry)
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Diterpenes (chemistry, pharmacology)
• Dose-Response Relationship, Drug
• HL-60 Cells
• HSP90 Heat-Shock Proteins (antagonists & inhibitors)
• Humans
• K562 Cells
• Leukemia (metabolism)
• Mitochondria (drug effects, metabolism)