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

Kwak CH, Lee SH, Lee SK, Ha SH, Suh SJ, Kwon KM, Chung TW, Ha KT, Chang YC, Lee YC, Kim DS, Chang HW, Kim CH - Mar Drugs (2015)

Bottom Line: 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.To the best of our knowledge, this is the first observation that ESM has anti-tumor activity in human cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Science, Sungkyunkwan University, Chunchun-Dong 300, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, Korea. hahaaaa@nate.com.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of the mechanisms of ESM-mediated apoptosis.
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marinedrugs-13-03936-f006: Schematic diagram of the mechanisms of ESM-mediated apoptosis.

Mentions: In the present study, to extend the pharmacological capacities of eel extracts, we successfully isolated and partially purified the ESM. For the first time, we demonstrated that the ESM triggers apoptotic cell death and inhibits cell proliferation in human leukemic K562 cells (Figure 1 and Figure 2). Our results have clearly shown that the cleaved forms of caspase-9, caspase-3 and PARP were also found to be increased in dose-dependent manners (Figure 3A,B). In addition, the expression of Bax and release of cytochrome C into the cytoplasm, as apoptotic signals, were dose-dependently increased by treatment of K562 cells with ESM (Figure 3C–E). Furthermore, phosphorylation levels of ERK1/2 and p38 in ESM-treated K562 cells were increased (Figure 4A). When cells were co-treated with ESM and inhibitor of ERK1/2 or p38, the cell viabilities were increased (Figure 4B). These results suggest that ESM induce apoptosis via activations of ERK1/2 and p38. Interestingly, when the K562 cells were co-treated with lactose, the reduction of cell viability due to ESM treatment was recovered (Figure 5). These findings suggest that lactose-binding molecules in ESM are likely the factors inducing apoptosis in K562 cells, as summarized in Figure 6. It is considered that ESM has similar protein properties compared with the lectins of other groups (Figure 1A) [13,14]. Thus, these molecules should be further studied. Our findings may provide a new drug candidate as an alternative therapy for human leukemia in the future.


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

Kwak CH, Lee SH, Lee SK, Ha SH, Suh SJ, Kwon KM, Chung TW, Ha KT, Chang YC, Lee YC, Kim DS, Chang HW, Kim CH - Mar Drugs (2015)

Schematic diagram of the mechanisms of ESM-mediated apoptosis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4483664&req=5

marinedrugs-13-03936-f006: Schematic diagram of the mechanisms of ESM-mediated apoptosis.
Mentions: In the present study, to extend the pharmacological capacities of eel extracts, we successfully isolated and partially purified the ESM. For the first time, we demonstrated that the ESM triggers apoptotic cell death and inhibits cell proliferation in human leukemic K562 cells (Figure 1 and Figure 2). Our results have clearly shown that the cleaved forms of caspase-9, caspase-3 and PARP were also found to be increased in dose-dependent manners (Figure 3A,B). In addition, the expression of Bax and release of cytochrome C into the cytoplasm, as apoptotic signals, were dose-dependently increased by treatment of K562 cells with ESM (Figure 3C–E). Furthermore, phosphorylation levels of ERK1/2 and p38 in ESM-treated K562 cells were increased (Figure 4A). When cells were co-treated with ESM and inhibitor of ERK1/2 or p38, the cell viabilities were increased (Figure 4B). These results suggest that ESM induce apoptosis via activations of ERK1/2 and p38. Interestingly, when the K562 cells were co-treated with lactose, the reduction of cell viability due to ESM treatment was recovered (Figure 5). These findings suggest that lactose-binding molecules in ESM are likely the factors inducing apoptosis in K562 cells, as summarized in Figure 6. It is considered that ESM has similar protein properties compared with the lectins of other groups (Figure 1A) [13,14]. Thus, these molecules should be further studied. Our findings may provide a new drug candidate as an alternative therapy for human leukemia in the future.

Bottom Line: 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.To the best of our knowledge, this is the first observation that ESM has anti-tumor activity in human cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Science, Sungkyunkwan University, Chunchun-Dong 300, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, Korea. hahaaaa@nate.com.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus