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Sea Hare Hydrolysate-Induced Reduction of Human Non-Small Cell Lung Cancer Cell Growth through Regulation of Macrophage Polarization and Non-Apoptotic Regulated Cell Death Pathways

Sea hare-derived compounds induce macrophage activation and reduce asthmatic parameters in mouse models of allergic asthma. These findings led us to study the role of sea hare hydrolysates (SHH) in cancer pathophysiology. SHH treatment-induced M1 macrophage activation in RAW264.7 cells, peritoneal m...

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Autores principales: Nyiramana, Marie Merci, Cho, Soo Buem, Kim, Eun-Jin, Kim, Min Jun, Ryu, Ji Hyeon, Nam, Hyun Jae, Kim, Nam-Gil, Park, Si-Hyang, Choi, Yeung Joon, Kang, Sang Soo, Jung, Myunghwan, Shin, Min-Kyoung, Han, Jaehee, Jang, In-Seok, Kang, Dawon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140097/
https://www.ncbi.nlm.nih.gov/pubmed/32204484
http://dx.doi.org/10.3390/cancers12030726
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author Nyiramana, Marie Merci
Cho, Soo Buem
Kim, Eun-Jin
Kim, Min Jun
Ryu, Ji Hyeon
Nam, Hyun Jae
Kim, Nam-Gil
Park, Si-Hyang
Choi, Yeung Joon
Kang, Sang Soo
Jung, Myunghwan
Shin, Min-Kyoung
Han, Jaehee
Jang, In-Seok
Kang, Dawon
author_facet Nyiramana, Marie Merci
Cho, Soo Buem
Kim, Eun-Jin
Kim, Min Jun
Ryu, Ji Hyeon
Nam, Hyun Jae
Kim, Nam-Gil
Park, Si-Hyang
Choi, Yeung Joon
Kang, Sang Soo
Jung, Myunghwan
Shin, Min-Kyoung
Han, Jaehee
Jang, In-Seok
Kang, Dawon
author_sort Nyiramana, Marie Merci
collection PubMed
description Sea hare-derived compounds induce macrophage activation and reduce asthmatic parameters in mouse models of allergic asthma. These findings led us to study the role of sea hare hydrolysates (SHH) in cancer pathophysiology. SHH treatment-induced M1 macrophage activation in RAW264.7 cells, peritoneal macrophages, and THP-1 cells, as did lipopolysaccharide (LPS) (+ INF-γ), whereas SHH reduced interleukin (IL)-4 (+IL-13)-induced M2 macrophage polarization. In addition, SHH treatment inhibited the actions of M1 and M2 macrophages, which have anticancer and pro-cancer effects, respectively, in non-small cell lung cancer cells (A549 and HCC-366) and tumor-associated macrophages (TAMs). Furthermore, SHH induced G2/M phase arrest and cell death in A549 cells. SHH also downregulated STAT3 activation in macrophages and A549 cells, and the down-regulation was recovered by colivelin, a STAT3 activator. SHH-induced reduction of M2 polarization and tumor growth was blocked by colivelin treatment. SHH-induced cell death did not occur in the manner of apoptotic signaling pathways, while the death pattern was mediated through pyroptosis/necroptosis, which causes membrane rupture, formation of vacuoles and bleb, activation of caspase-1, and secretion of IL-1β in SHH-treated A549 cells. However, a combination of SHH and colivelin blocked caspase-1 activation. Z-YVAD-FMK and necrostatin-1, pyrotosis and necroptosis inhibitors, attenuated SHH’s effect on the cell viability of A549 cells. Taken together, SHH showed anticancer effects through a cytotoxic effect on A549 cells and a regulatory effect on macrophages in A549 cells. In addition, the SHH-induced anticancer effects were mediated by non-apoptotic regulated cell death pathways under STAT3 inhibition. These results suggest that SHH may be offered as a potential remedy for cancer immunotherapy.
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spelling pubmed-71400972020-04-13 Sea Hare Hydrolysate-Induced Reduction of Human Non-Small Cell Lung Cancer Cell Growth through Regulation of Macrophage Polarization and Non-Apoptotic Regulated Cell Death Pathways Nyiramana, Marie Merci Cho, Soo Buem Kim, Eun-Jin Kim, Min Jun Ryu, Ji Hyeon Nam, Hyun Jae Kim, Nam-Gil Park, Si-Hyang Choi, Yeung Joon Kang, Sang Soo Jung, Myunghwan Shin, Min-Kyoung Han, Jaehee Jang, In-Seok Kang, Dawon Cancers (Basel) Article Sea hare-derived compounds induce macrophage activation and reduce asthmatic parameters in mouse models of allergic asthma. These findings led us to study the role of sea hare hydrolysates (SHH) in cancer pathophysiology. SHH treatment-induced M1 macrophage activation in RAW264.7 cells, peritoneal macrophages, and THP-1 cells, as did lipopolysaccharide (LPS) (+ INF-γ), whereas SHH reduced interleukin (IL)-4 (+IL-13)-induced M2 macrophage polarization. In addition, SHH treatment inhibited the actions of M1 and M2 macrophages, which have anticancer and pro-cancer effects, respectively, in non-small cell lung cancer cells (A549 and HCC-366) and tumor-associated macrophages (TAMs). Furthermore, SHH induced G2/M phase arrest and cell death in A549 cells. SHH also downregulated STAT3 activation in macrophages and A549 cells, and the down-regulation was recovered by colivelin, a STAT3 activator. SHH-induced reduction of M2 polarization and tumor growth was blocked by colivelin treatment. SHH-induced cell death did not occur in the manner of apoptotic signaling pathways, while the death pattern was mediated through pyroptosis/necroptosis, which causes membrane rupture, formation of vacuoles and bleb, activation of caspase-1, and secretion of IL-1β in SHH-treated A549 cells. However, a combination of SHH and colivelin blocked caspase-1 activation. Z-YVAD-FMK and necrostatin-1, pyrotosis and necroptosis inhibitors, attenuated SHH’s effect on the cell viability of A549 cells. Taken together, SHH showed anticancer effects through a cytotoxic effect on A549 cells and a regulatory effect on macrophages in A549 cells. In addition, the SHH-induced anticancer effects were mediated by non-apoptotic regulated cell death pathways under STAT3 inhibition. These results suggest that SHH may be offered as a potential remedy for cancer immunotherapy. MDPI 2020-03-19 /pmc/articles/PMC7140097/ /pubmed/32204484 http://dx.doi.org/10.3390/cancers12030726 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nyiramana, Marie Merci
Cho, Soo Buem
Kim, Eun-Jin
Kim, Min Jun
Ryu, Ji Hyeon
Nam, Hyun Jae
Kim, Nam-Gil
Park, Si-Hyang
Choi, Yeung Joon
Kang, Sang Soo
Jung, Myunghwan
Shin, Min-Kyoung
Han, Jaehee
Jang, In-Seok
Kang, Dawon
Sea Hare Hydrolysate-Induced Reduction of Human Non-Small Cell Lung Cancer Cell Growth through Regulation of Macrophage Polarization and Non-Apoptotic Regulated Cell Death Pathways
title Sea Hare Hydrolysate-Induced Reduction of Human Non-Small Cell Lung Cancer Cell Growth through Regulation of Macrophage Polarization and Non-Apoptotic Regulated Cell Death Pathways
title_full Sea Hare Hydrolysate-Induced Reduction of Human Non-Small Cell Lung Cancer Cell Growth through Regulation of Macrophage Polarization and Non-Apoptotic Regulated Cell Death Pathways
title_fullStr Sea Hare Hydrolysate-Induced Reduction of Human Non-Small Cell Lung Cancer Cell Growth through Regulation of Macrophage Polarization and Non-Apoptotic Regulated Cell Death Pathways
title_full_unstemmed Sea Hare Hydrolysate-Induced Reduction of Human Non-Small Cell Lung Cancer Cell Growth through Regulation of Macrophage Polarization and Non-Apoptotic Regulated Cell Death Pathways
title_short Sea Hare Hydrolysate-Induced Reduction of Human Non-Small Cell Lung Cancer Cell Growth through Regulation of Macrophage Polarization and Non-Apoptotic Regulated Cell Death Pathways
title_sort sea hare hydrolysate-induced reduction of human non-small cell lung cancer cell growth through regulation of macrophage polarization and non-apoptotic regulated cell death pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140097/
https://www.ncbi.nlm.nih.gov/pubmed/32204484
http://dx.doi.org/10.3390/cancers12030726
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