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Mar. Drugs 2015, 13(6), 3936-3949;

Induction of Apoptosis and Antitumor Activity of Eel Skin Mucus, Containing Lactose-Binding Molecules, on Human Leukemic K562 Cells

Department of Biological Science, Sungkyunkwan University, Chunchun-Dong 300, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, Korea
Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-Do 626-770, Korea
Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Korea
College of Natural Resources and Life Science, Dong-A University, Busan, 604-714, Korea
Department of Food Science and Biotechnology, Kyung Sung University, Nam-Gu, Busan, 608-736, Korea
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea
Authors to whom correspondence should be addressed.
Academic Editor: Antonio Trincone
Received: 5 March 2015 / Revised: 2 June 2015 / Accepted: 5 June 2015 / Published: 19 June 2015
(This article belongs to the Special Issue Marine Glycoconjugates)
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For innate immune defense, lower animals such as fish and amphibian are covered with skin mucus, which acts as both a mechanical and biochemical barrier. Although several mucus sources have been isolated and studied for their biochemical and immunological functions, the precise mechanism(s) of action remains unknown. In the present study, we additionally found the eel skin mucus (ESM) to be a promising candidate for use in anti-tumor therapy. Our results showed that the viability of K562 cells was decreased in a dose-dependent manner by treatment with the isolated ESM. The cleaved forms of caspase-9, caspase-3 and poly adenosine diphosphate-ribose polymerase were increased by ESM. The levels of Bax expression and released cytochrome C were also increased after treatment with ESM. Furthermore, during the ESM mediated-apoptosis, phosphorylation levels of ERK1/2 and p38 but not JNK were increased and cell viabilities of the co-treated cells with ESM and inhibitors of ERK 1/2 or p38 were also increased. In addition, treatment with lactose rescued the ESM-mediated decrease in cell viability, indicating lactose-containing glycans in the leukemia cells acted as a counterpart of the ESM for interaction. Taken together, these results suggest that ESM could induce mitochondria-mediated apoptosis through membrane interaction of the K562 human leukemia cells. To the best of our knowledge, this is the first observation that ESM has anti-tumor activity in human cells. View Full-Text
Keywords: mucus; Anguilla japonica; apoptosis; lectin-like protein; glycan mucus; Anguilla japonica; apoptosis; lectin-like protein; glycan

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Kwak, C.-H.; Lee, S.-H.; Lee, S.-K.; Ha, S.-H.; Suh, S.-J.; Kwon, K.-M.; Chung, T.-W.; Ha, K.-T.; Chang, Y.-C.; Lee, Y.-C.; Kim, D.-S.; Chang, H.-W.; Kim, C.-H. Induction of Apoptosis and Antitumor Activity of Eel Skin Mucus, Containing Lactose-Binding Molecules, on Human Leukemic K562 Cells. Mar. Drugs 2015, 13, 3936-3949.

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