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

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2013 Mar 6

PMID 23459302

Citations 14

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

Affiliations

Soon will be listed here.

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.

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