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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

ESM induces apoptosis signaling pathway in K562 cells. ESM-treated cells were analyzed by immunoblotting with antibodies against cleaved PARP (C-PARP, 89 kDa), full length PARP (116 kDa), cleaved caspase-3 (C-Cas-3) and cleaved caspase-9 (C-Cas-9). (A) Levels of Bax and Bcl-2 expression were then determined by immunoblotting analysis (C); The bar chart shows densitometric analysis of the indicated bands in A and C, respectively (B,D); Cytochrome C (Cyt C) in the cytosolic fractions was detected by immunoblotting (E). β-Actin and GAPDH were used as the internal controls. Data are presented as the mean ± SEM (n = 3). ** P <0.01 and * P < 0.05 compared with control.
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marinedrugs-13-03936-f003: ESM induces apoptosis signaling pathway in K562 cells. ESM-treated cells were analyzed by immunoblotting with antibodies against cleaved PARP (C-PARP, 89 kDa), full length PARP (116 kDa), cleaved caspase-3 (C-Cas-3) and cleaved caspase-9 (C-Cas-9). (A) Levels of Bax and Bcl-2 expression were then determined by immunoblotting analysis (C); The bar chart shows densitometric analysis of the indicated bands in A and C, respectively (B,D); Cytochrome C (Cyt C) in the cytosolic fractions was detected by immunoblotting (E). β-Actin and GAPDH were used as the internal controls. Data are presented as the mean ± SEM (n = 3). ** P <0.01 and * P < 0.05 compared with control.

Mentions: To confirm the apoptosis signaling pathways regulated by ESM, investigation of the apoptosis signaling pathways was carried out next. As shown in Figure 3A, when K562 cells were treated with ESM, the cleaved forms of PARP, caspase-3 and caspase-9 were increased. In addition, the Bax expression was also increased in a dose-dependent manner (Figure 3C). However, the expression of Bcl-2, a representative anti-apoptotic signaling protein, was not changed. Furthermore, the amounts of cytochrome c released to the cytosol displayed a dramatic increase after treatment with ESM at the 100 and 500 μg/mL concentrations (Figure 3E). Taken together, these results again support that ESM induces apoptosis in K562 cells.


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)

ESM induces apoptosis signaling pathway in K562 cells. ESM-treated cells were analyzed by immunoblotting with antibodies against cleaved PARP (C-PARP, 89 kDa), full length PARP (116 kDa), cleaved caspase-3 (C-Cas-3) and cleaved caspase-9 (C-Cas-9). (A) Levels of Bax and Bcl-2 expression were then determined by immunoblotting analysis (C); The bar chart shows densitometric analysis of the indicated bands in A and C, respectively (B,D); Cytochrome C (Cyt C) in the cytosolic fractions was detected by immunoblotting (E). β-Actin and GAPDH were used as the internal controls. Data are presented as the mean ± SEM (n = 3). ** P <0.01 and * P < 0.05 compared with control.
© Copyright Policy
Related In: Results  -  Collection

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

marinedrugs-13-03936-f003: ESM induces apoptosis signaling pathway in K562 cells. ESM-treated cells were analyzed by immunoblotting with antibodies against cleaved PARP (C-PARP, 89 kDa), full length PARP (116 kDa), cleaved caspase-3 (C-Cas-3) and cleaved caspase-9 (C-Cas-9). (A) Levels of Bax and Bcl-2 expression were then determined by immunoblotting analysis (C); The bar chart shows densitometric analysis of the indicated bands in A and C, respectively (B,D); Cytochrome C (Cyt C) in the cytosolic fractions was detected by immunoblotting (E). β-Actin and GAPDH were used as the internal controls. Data are presented as the mean ± SEM (n = 3). ** P <0.01 and * P < 0.05 compared with control.
Mentions: To confirm the apoptosis signaling pathways regulated by ESM, investigation of the apoptosis signaling pathways was carried out next. As shown in Figure 3A, when K562 cells were treated with ESM, the cleaved forms of PARP, caspase-3 and caspase-9 were increased. In addition, the Bax expression was also increased in a dose-dependent manner (Figure 3C). However, the expression of Bcl-2, a representative anti-apoptotic signaling protein, was not changed. Furthermore, the amounts of cytochrome c released to the cytosol displayed a dramatic increase after treatment with ESM at the 100 and 500 μg/mL concentrations (Figure 3E). Taken together, these results again support that ESM induces apoptosis in K562 cells.

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