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The Blockade of Mitogen-Activated Protein Kinase 14 Activation by Marine Natural Product Crassolide Triggers ICD in Tumor Cells and Stimulates Anti-Tumor Immunity

Immunogenic cell death (ICD) refers to a type of cell death that stimulates immune responses. It is characterized by the surface exposure of damage-associated molecular patterns (DAMPs), which can facilitate the uptake of antigens by dendritic cells (DCs) and stimulate DC activation, resulting in T...

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Autores principales: Tsai, Keng-Chang, Chen, Chia-Sheng, Su, Jui-Hsin, Lee, Yu-Ching, Tseng, Yu-Hwei, Wei, Wen-Chi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141386/
https://www.ncbi.nlm.nih.gov/pubmed/37103364
http://dx.doi.org/10.3390/md21040225
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author Tsai, Keng-Chang
Chen, Chia-Sheng
Su, Jui-Hsin
Lee, Yu-Ching
Tseng, Yu-Hwei
Wei, Wen-Chi
author_facet Tsai, Keng-Chang
Chen, Chia-Sheng
Su, Jui-Hsin
Lee, Yu-Ching
Tseng, Yu-Hwei
Wei, Wen-Chi
author_sort Tsai, Keng-Chang
collection PubMed
description Immunogenic cell death (ICD) refers to a type of cell death that stimulates immune responses. It is characterized by the surface exposure of damage-associated molecular patterns (DAMPs), which can facilitate the uptake of antigens by dendritic cells (DCs) and stimulate DC activation, resulting in T cell immunity. The activation of immune responses through ICD has been proposed as a promising approach for cancer immunotherapy. The marine natural product crassolide, a cembranolide isolated from the Formosan soft coral Lobophytum michaelae, has been shown to have cytotoxic effects on cancer cells. In this study, we investigated the effects of crassolide on the induction of ICD, the expression of immune checkpoint molecules and cell adhesion molecules, as well as tumor growth in a murine 4T1 mammary carcinoma model. Immunofluorescence staining for DAMP ectolocalization, Western blotting for protein expression and Z′-LYTE kinase assay for kinase activity were performed. The results showed that crassolide significantly increased ICD and slightly decreased the expression level of CD24 on the surface of murine mammary carcinoma cells. An orthotopic tumor engraftment of 4T1 carcinoma cells indicated that crassolide-treated tumor cell lysates stimulate anti-tumor immunity against tumor growth. Crassolide was also found to be a blocker of mitogen-activated protein kinase 14 activation. This study highlights the immunotherapeutic effects of crassolide on the activation of anticancer immune responses and suggests the potential clinical use of crassolide as a novel treatment for breast cancer.
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spelling pubmed-101413862023-04-29 The Blockade of Mitogen-Activated Protein Kinase 14 Activation by Marine Natural Product Crassolide Triggers ICD in Tumor Cells and Stimulates Anti-Tumor Immunity Tsai, Keng-Chang Chen, Chia-Sheng Su, Jui-Hsin Lee, Yu-Ching Tseng, Yu-Hwei Wei, Wen-Chi Mar Drugs Article Immunogenic cell death (ICD) refers to a type of cell death that stimulates immune responses. It is characterized by the surface exposure of damage-associated molecular patterns (DAMPs), which can facilitate the uptake of antigens by dendritic cells (DCs) and stimulate DC activation, resulting in T cell immunity. The activation of immune responses through ICD has been proposed as a promising approach for cancer immunotherapy. The marine natural product crassolide, a cembranolide isolated from the Formosan soft coral Lobophytum michaelae, has been shown to have cytotoxic effects on cancer cells. In this study, we investigated the effects of crassolide on the induction of ICD, the expression of immune checkpoint molecules and cell adhesion molecules, as well as tumor growth in a murine 4T1 mammary carcinoma model. Immunofluorescence staining for DAMP ectolocalization, Western blotting for protein expression and Z′-LYTE kinase assay for kinase activity were performed. The results showed that crassolide significantly increased ICD and slightly decreased the expression level of CD24 on the surface of murine mammary carcinoma cells. An orthotopic tumor engraftment of 4T1 carcinoma cells indicated that crassolide-treated tumor cell lysates stimulate anti-tumor immunity against tumor growth. Crassolide was also found to be a blocker of mitogen-activated protein kinase 14 activation. This study highlights the immunotherapeutic effects of crassolide on the activation of anticancer immune responses and suggests the potential clinical use of crassolide as a novel treatment for breast cancer. MDPI 2023-03-31 /pmc/articles/PMC10141386/ /pubmed/37103364 http://dx.doi.org/10.3390/md21040225 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tsai, Keng-Chang
Chen, Chia-Sheng
Su, Jui-Hsin
Lee, Yu-Ching
Tseng, Yu-Hwei
Wei, Wen-Chi
The Blockade of Mitogen-Activated Protein Kinase 14 Activation by Marine Natural Product Crassolide Triggers ICD in Tumor Cells and Stimulates Anti-Tumor Immunity
title The Blockade of Mitogen-Activated Protein Kinase 14 Activation by Marine Natural Product Crassolide Triggers ICD in Tumor Cells and Stimulates Anti-Tumor Immunity
title_full The Blockade of Mitogen-Activated Protein Kinase 14 Activation by Marine Natural Product Crassolide Triggers ICD in Tumor Cells and Stimulates Anti-Tumor Immunity
title_fullStr The Blockade of Mitogen-Activated Protein Kinase 14 Activation by Marine Natural Product Crassolide Triggers ICD in Tumor Cells and Stimulates Anti-Tumor Immunity
title_full_unstemmed The Blockade of Mitogen-Activated Protein Kinase 14 Activation by Marine Natural Product Crassolide Triggers ICD in Tumor Cells and Stimulates Anti-Tumor Immunity
title_short The Blockade of Mitogen-Activated Protein Kinase 14 Activation by Marine Natural Product Crassolide Triggers ICD in Tumor Cells and Stimulates Anti-Tumor Immunity
title_sort blockade of mitogen-activated protein kinase 14 activation by marine natural product crassolide triggers icd in tumor cells and stimulates anti-tumor immunity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141386/
https://www.ncbi.nlm.nih.gov/pubmed/37103364
http://dx.doi.org/10.3390/md21040225
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