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Journal of Cancer Research and Clinical Oncology

, Volume 141, Issue 2, pp 255–268 | Cite as

Dieckol, isolated from the edible brown algae Ecklonia cava, induces apoptosis of ovarian cancer cells and inhibits tumor xenograft growth

  • Ji-Hye Ahn
  • Yeong-In Yang
  • Kyung-Tae Lee
  • Jung-Hye ChoiEmail author
Original Article – Cancer Research

Abstract

Purpose

Ecklonia cava is an abundant brown alga and has been reported to possess various bioactive compounds having anti-inflammatory effect. However, the anticancer effects of dieckol, a major active compound in E. cava, are poorly understood. In the present study, we investigated the anti-tumor activity of dieckol and its molecular mechanism in ovarian cancer cells and in a xenograft mouse model .

Methods

MTT assay, PI staining, and PI and Annexin double staining were performed to study cell cytotoxicity, cell cycle distribution, and apoptosis. We also investigated reactive oxygen species (ROS) production and protein expression using flow cytometry and Western blot analysis, respectively. Anti-tumor effects of dieckol were evaluated in SKOV3 tumor xenograft model.

Results

We found that the E. cava extract and its phlorotannins have cytotoxic effects on A2780 and SKOV3 ovarian cancer cells. Dieckol induced the apoptosis of SKOV3 cells and suppressed tumor growth without any significant adverse effect in the SKOV3-bearing mouse model. Dieckol triggered the activation of caspase-8, caspase-9, and caspase-3, and pretreatment with caspase inhibitors neutralized the pro-apoptotic activity of dieckol. Furthermore, treatment with dieckol caused mitochondrial dysfunction and suppressed the levels of anti-apoptotic proteins. We further demonstrated that dieckol induced an increase in intracellular ROS, and the antioxidant N-acetyl-l-cysteine (NAC) significantly reversed the caspase activation, cytochrome c release, Bcl-2 downregulation, and apoptosis that were caused by dieckol. Moreover, dieckol inhibited the activity of AKT and p38, and overexpression of AKT and p38, at least in part, reversed dieckol-induced apoptosis in SKOV3 cells.

Conclusion

These data suggest that dieckol suppresses ovarian cancer cell growth by inducing caspase-dependent apoptosis via ROS production and the regulation of AKT and p38 signaling.

Keywords

Apoptosis Ecklonia cava Dieckol Ovarian cancer Reactive oxygen species Tumor xenograft model 

Notes

Acknowledgments

This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant (to JHC) funded by the Korea government (MEST) (2012R1A1A2039648 and 2010-0004306).

Conflict of interest

The authors have declared no conflict of interest.

Supplementary material

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Supplementary material 1 (TIFF 1558 kb)
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Supplementary material 2 (TIFF 798 kb)
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Supplementary material 3 (TIFF 154 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ji-Hye Ahn
    • 1
    • 2
  • Yeong-In Yang
    • 1
    • 2
  • Kyung-Tae Lee
    • 1
  • Jung-Hye Choi
    • 1
    • 2
    Email author
  1. 1.Department of Life and Nanopharmaceutical ScienceKyung Hee UniversitySeoulRepublic of Korea
  2. 2.Division of Molecular Biology, College of PharmacyKyung Hee UniversitySeoulRepublic of Korea

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