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Evidence-Based Complementary and Alternative Medicine
Volume 2017, Article ID 2752716, 12 pages
Research Article

Anticancer Effect of Nemopilema nomurai Jellyfish Venom on HepG2 Cells and a Tumor Xenograft Animal Model

1Institute of Animal Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea
2College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea
3Department of Anatomy, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea
4Headquarters for Marine Environment, National Fisheries Research & Development Institute, Shiran-ri, Gijang-eup, Gijang-gun, Busan 619-705, Republic of Korea

Correspondence should be addressed to Euikyung Kim;

Received 2 February 2017; Accepted 5 June 2017; Published 13 July 2017

Academic Editor: Youn C. Kim

Copyright © 2017 Hyunkyoung Lee et al. 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.


Various kinds of animal venoms and their components have been widely studied for potential therapeutic applications. This study evaluated whether Nemopilema nomurai jellyfish venom (NnV) has anticancer activity. NnV strongly induced cytotoxicity of HepG2 cells through apoptotic cell death, as demonstrated by alterations of chromatic morphology, activation of procaspase-3, and an increase in the Bax/Bcl-2 ratio. Furthermore, NnV inhibited the phosphorylation of PI3K, PDK1, Akt, mTOR, p70S6K, and 4EBP1, whereas it enhanced the expression of p-PTEN. Interestingly, NnV also inactivated the negative feedback loops associated with Akt activation, as demonstrated by downregulation of Akt at Ser473 and mTOR at Ser2481. The anticancer effect of NnV was significant in a HepG2 xenograft mouse model, with no obvious toxicity. HepG2 cell death by NnV was inhibited by tetracycline, metalloprotease inhibitor, suggesting that metalloprotease component in NnV is closely related to the anticancer effects. This study demonstrates, for the first time, that NnV exerts highly selective cytotoxicity in HepG2 cells via dual inhibition of the Akt and mTOR signaling pathways, but not in normal cells.