Next Article in Journal
The Activating NKG2C Receptor Is Significantly Reduced in NK Cells after Allogeneic Stem Cell Transplantation in Patients with Severe Graft-versus-Host Disease
Next Article in Special Issue
Role of IRE1α/XBP-1 in Cystic Fibrosis Airway Inflammation
Previous Article in Journal
Comparative Proteomic and Physiological Analysis Reveals the Variation Mechanisms of Leaf Coloration and Carbon Fixation in a Xantha Mutant of Ginkgo biloba L.
Previous Article in Special Issue
Relevance of Endoplasmic Reticulum Stress Cell Signaling in Liver Cold Ischemia Reperfusion Injury
Article Menu
Issue 11 (November) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(11), 1787; doi:10.3390/ijms17111787

Cytotoxicity of 11-epi-Sinulariolide Acetate Isolated from Cultured Soft Corals on HA22T Cells through the Endoplasmic Reticulum Stress Pathway and Mitochondrial Dysfunction

Graduate Institute of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan
Department of Biomedical Sciences and Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
Division of Pediatric Infectious Disease, Department of Pediatrics, Chang Gung Memorial Hospital, Linkuo 33305, Taiwan
Department of Food Science and Nutrition, Meiho University, Pingtung 91202, Taiwan
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Department of Beauty Science, Meiho University, Pingtung 91202, Taiwan
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editor: Masato Matsuoka
Received: 2 May 2016 / Revised: 29 August 2016 / Accepted: 12 October 2016 / Published: 27 October 2016
(This article belongs to the Special Issue Modulators of Endoplasmic Reticulum Stress 2016)
View Full-Text   |   Download PDF [5652 KB, uploaded 27 October 2016]   |  


Natural compounds from soft corals have been increasingly used for their antitumor therapeutic properties. This study examined 11-epi-sinulariolide acetate (11-epi-SA), an active compound isolated from the cultured soft coral Sinularia flexibilis, to determine its potential antitumor effect on four hepatocellular carcinoma cell lines. Cell viability was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the results demonstrated that 11-epi-SA treatment showed more cytotoxic effect toward HA22T cells. Protein profiling of the 11-epi-SA-treated HA22T cells revealed substantial protein alterations associated with stress response and protein synthesis and folding, suggesting that the mitochondria and endoplasmic reticulum (ER) play roles in 11-epi-SA-initiated apoptosis. Moreover, 11-epi-SA activated caspase-dependent apoptotic cell death, suggesting that mitochondria-related apoptosis genes were involved in programmed cell death. The unfolded protein response signaling pathway-related proteins were also activated on 11-epi-SA treatment, and these changes were accompanied by the upregulated expression of growth arrest and DNA damage-inducible protein (GADD153) and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP), the genes encoding transcription factors associated with growth arrest and apoptosis under prolonged ER stress. Two inhibitors, namely salubrinal (Sal) and SP600125, partially abrogated 11-epi-SA-related cell death, implying that the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)–activating transcription factor (ATF) 6–CHOP or the inositol-requiring enzyme 1 alpha (IRE1α)–c-Jun N-terminal kinase (JNK)–cJun signal pathway was activated after 11-epi-SA treatment. In general, these results suggest that 11-epi-SA exerts cytotoxic effects on HA22T cells through mitochondrial dysfunction and ER stress cell death pathways. View Full-Text
Keywords: 11-epi-sinulariolide acetate; mitochondrial dysfunction; ER stress; antitumor; hepatocellular carcinoma 11-epi-sinulariolide acetate; mitochondrial dysfunction; ER stress; antitumor; hepatocellular carcinoma

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Lin, J.-J.; Wang, R.Y.L.; Chen, J.-C.; Chiu, C.-C.; Liao, M.-H.; Wu, Y.-J. Cytotoxicity of 11-epi-Sinulariolide Acetate Isolated from Cultured Soft Corals on HA22T Cells through the Endoplasmic Reticulum Stress Pathway and Mitochondrial Dysfunction. Int. J. Mol. Sci. 2016, 17, 1787.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top