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

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 actio...

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Main Authors: Choong-Hwan Kwak, Sook-Hyun Lee, Sung-Kyun Lee, Sun-Hyung Ha, Seok-Jong Suh, Kyung-Min Kwon, Tae-Wook Chung, Ki-Tae Ha, Young-Chae Chang, Young-Choon Lee, Dong-Soo Kim, Hyeun-Wook Chang, Cheorl-Ho Kim
Format: Article
Language:English
Published: MDPI AG 2015-06-01
Series:Marine Drugs
Subjects:
Online Access:http://www.mdpi.com/1660-3397/13/6/3936
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author Choong-Hwan Kwak
Sook-Hyun Lee
Sung-Kyun Lee
Sun-Hyung Ha
Seok-Jong Suh
Kyung-Min Kwon
Tae-Wook Chung
Ki-Tae Ha
Young-Chae Chang
Young-Choon Lee
Dong-Soo Kim
Hyeun-Wook Chang
Cheorl-Ho Kim
author_facet Choong-Hwan Kwak
Sook-Hyun Lee
Sung-Kyun Lee
Sun-Hyung Ha
Seok-Jong Suh
Kyung-Min Kwon
Tae-Wook Chung
Ki-Tae Ha
Young-Chae Chang
Young-Choon Lee
Dong-Soo Kim
Hyeun-Wook Chang
Cheorl-Ho Kim
author_sort Choong-Hwan Kwak
collection DOAJ
description 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.
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spelling doaj.art-e08fddeb3db5431a81653746ce03ad072022-12-22T02:07:00ZengMDPI AGMarine Drugs1660-33972015-06-011363936394910.3390/md13063936md13063936Induction of Apoptosis and Antitumor Activity of Eel Skin Mucus, Containing Lactose-Binding Molecules, on Human Leukemic K562 CellsChoong-Hwan Kwak0Sook-Hyun Lee1Sung-Kyun Lee2Sun-Hyung Ha3Seok-Jong Suh4Kyung-Min Kwon5Tae-Wook Chung6Ki-Tae Ha7Young-Chae Chang8Young-Choon Lee9Dong-Soo Kim10Hyeun-Wook Chang11Cheorl-Ho Kim12Department of Biological Science, Sungkyunkwan University, Chunchun-Dong 300, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, KoreaDepartment of Biological Science, Sungkyunkwan University, Chunchun-Dong 300, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, KoreaDepartment of Biological Science, Sungkyunkwan University, Chunchun-Dong 300, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, KoreaDepartment of Biological Science, Sungkyunkwan University, Chunchun-Dong 300, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, KoreaDepartment of Biological Science, Sungkyunkwan University, Chunchun-Dong 300, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, KoreaDepartment of Biological Science, Sungkyunkwan University, Chunchun-Dong 300, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, KoreaDivision of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-Do 626-770, KoreaDivision of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-Do 626-770, KoreaResearch Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, KoreaCollege of Natural Resources and Life Science, Dong-A University, Busan, 604-714, KoreaDepartment of Food Science and Biotechnology, Kyung Sung University, Nam-Gu, Busan, 608-736, KoreaCollege of Pharmacy, Yeungnam University, Gyeongsan 712-749, KoreaDepartment of Biological Science, Sungkyunkwan University, Chunchun-Dong 300, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, KoreaFor 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.http://www.mdpi.com/1660-3397/13/6/3936mucusAnguilla japonicaapoptosislectin-like proteinglycan
spellingShingle Choong-Hwan Kwak
Sook-Hyun Lee
Sung-Kyun Lee
Sun-Hyung Ha
Seok-Jong Suh
Kyung-Min Kwon
Tae-Wook Chung
Ki-Tae Ha
Young-Chae Chang
Young-Choon Lee
Dong-Soo Kim
Hyeun-Wook Chang
Cheorl-Ho Kim
Induction of Apoptosis and Antitumor Activity of Eel Skin Mucus, Containing Lactose-Binding Molecules, on Human Leukemic K562 Cells
Marine Drugs
mucus
Anguilla japonica
apoptosis
lectin-like protein
glycan
title Induction of Apoptosis and Antitumor Activity of Eel Skin Mucus, Containing Lactose-Binding Molecules, on Human Leukemic K562 Cells
title_full Induction of Apoptosis and Antitumor Activity of Eel Skin Mucus, Containing Lactose-Binding Molecules, on Human Leukemic K562 Cells
title_fullStr Induction of Apoptosis and Antitumor Activity of Eel Skin Mucus, Containing Lactose-Binding Molecules, on Human Leukemic K562 Cells
title_full_unstemmed Induction of Apoptosis and Antitumor Activity of Eel Skin Mucus, Containing Lactose-Binding Molecules, on Human Leukemic K562 Cells
title_short Induction of Apoptosis and Antitumor Activity of Eel Skin Mucus, Containing Lactose-Binding Molecules, on Human Leukemic K562 Cells
title_sort induction of apoptosis and antitumor activity of eel skin mucus containing lactose binding molecules on human leukemic k562 cells
topic mucus
Anguilla japonica
apoptosis
lectin-like protein
glycan
url http://www.mdpi.com/1660-3397/13/6/3936
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