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Autophagy Plays a Critical Role in ChLym-1-Induced Cytotoxicity of Non-Hodgkin’s Lymphoma Cells

Autophagy is a critical mechanism in both cancer therapy resistance and tumor suppression. Monoclonal antibodies have been documented to kill tumor cells via apoptosis, antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In this study, we report for the first...

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Autores principales: Fan, Jiajun, Zeng, Xian, Li, Yubin, Wang, Shaofei, Wang, Ziyu, Sun, Yun, Gao, Hongjian, Zhang, Guoping, Feng, Meiqing, Ju, Dianwen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756084/
https://www.ncbi.nlm.nih.gov/pubmed/24015249
http://dx.doi.org/10.1371/journal.pone.0072478
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author Fan, Jiajun
Zeng, Xian
Li, Yubin
Wang, Shaofei
Wang, Ziyu
Sun, Yun
Gao, Hongjian
Zhang, Guoping
Feng, Meiqing
Ju, Dianwen
author_facet Fan, Jiajun
Zeng, Xian
Li, Yubin
Wang, Shaofei
Wang, Ziyu
Sun, Yun
Gao, Hongjian
Zhang, Guoping
Feng, Meiqing
Ju, Dianwen
author_sort Fan, Jiajun
collection PubMed
description Autophagy is a critical mechanism in both cancer therapy resistance and tumor suppression. Monoclonal antibodies have been documented to kill tumor cells via apoptosis, antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In this study, we report for the first time that chLym-1, a chimeric anti-human HLA-DR monoclonal antibody, induces autophagy in Raji Non-Hodgkin’s Lymphoma (NHL) cells. Interestingly, inhibition of autophagy by pharmacological inhibitors (3-methyladenine and NH(4)Cl) or genetic approaches (siRNA targeting Atg5) suppresses chLym-1-induced growth inhibition, apoptosis, ADCC and CDC in Raji cells, while induction of autophagy could accelerate cytotoxic effects of chLym-1 on Raji cells. Furthermore, chLym-1-induced autophagy can mediate apoptosis through Caspase 9 activation, demonstrating the tumor-suppressing role of autophagy in antilymphoma effects of chLym-1. Moreover, chLym-1 can activate several upstream signaling pathways of autophagy including Akt/mTOR and extracellular signal-regulated kinase 1/2 (Erk1/2). These results elucidate the critical role of autophagy in cytotoxicity of chLym-1 antibody and suggest a potential therapeutic strategy of NHL therapy by monoclonal antibody chLym-1 in combination with autophagy inducer.
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spelling pubmed-37560842013-09-06 Autophagy Plays a Critical Role in ChLym-1-Induced Cytotoxicity of Non-Hodgkin’s Lymphoma Cells Fan, Jiajun Zeng, Xian Li, Yubin Wang, Shaofei Wang, Ziyu Sun, Yun Gao, Hongjian Zhang, Guoping Feng, Meiqing Ju, Dianwen PLoS One Research Article Autophagy is a critical mechanism in both cancer therapy resistance and tumor suppression. Monoclonal antibodies have been documented to kill tumor cells via apoptosis, antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In this study, we report for the first time that chLym-1, a chimeric anti-human HLA-DR monoclonal antibody, induces autophagy in Raji Non-Hodgkin’s Lymphoma (NHL) cells. Interestingly, inhibition of autophagy by pharmacological inhibitors (3-methyladenine and NH(4)Cl) or genetic approaches (siRNA targeting Atg5) suppresses chLym-1-induced growth inhibition, apoptosis, ADCC and CDC in Raji cells, while induction of autophagy could accelerate cytotoxic effects of chLym-1 on Raji cells. Furthermore, chLym-1-induced autophagy can mediate apoptosis through Caspase 9 activation, demonstrating the tumor-suppressing role of autophagy in antilymphoma effects of chLym-1. Moreover, chLym-1 can activate several upstream signaling pathways of autophagy including Akt/mTOR and extracellular signal-regulated kinase 1/2 (Erk1/2). These results elucidate the critical role of autophagy in cytotoxicity of chLym-1 antibody and suggest a potential therapeutic strategy of NHL therapy by monoclonal antibody chLym-1 in combination with autophagy inducer. Public Library of Science 2013-08-28 /pmc/articles/PMC3756084/ /pubmed/24015249 http://dx.doi.org/10.1371/journal.pone.0072478 Text en © 2013 Fan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Fan, Jiajun
Zeng, Xian
Li, Yubin
Wang, Shaofei
Wang, Ziyu
Sun, Yun
Gao, Hongjian
Zhang, Guoping
Feng, Meiqing
Ju, Dianwen
Autophagy Plays a Critical Role in ChLym-1-Induced Cytotoxicity of Non-Hodgkin’s Lymphoma Cells
title Autophagy Plays a Critical Role in ChLym-1-Induced Cytotoxicity of Non-Hodgkin’s Lymphoma Cells
title_full Autophagy Plays a Critical Role in ChLym-1-Induced Cytotoxicity of Non-Hodgkin’s Lymphoma Cells
title_fullStr Autophagy Plays a Critical Role in ChLym-1-Induced Cytotoxicity of Non-Hodgkin’s Lymphoma Cells
title_full_unstemmed Autophagy Plays a Critical Role in ChLym-1-Induced Cytotoxicity of Non-Hodgkin’s Lymphoma Cells
title_short Autophagy Plays a Critical Role in ChLym-1-Induced Cytotoxicity of Non-Hodgkin’s Lymphoma Cells
title_sort autophagy plays a critical role in chlym-1-induced cytotoxicity of non-hodgkin’s lymphoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756084/
https://www.ncbi.nlm.nih.gov/pubmed/24015249
http://dx.doi.org/10.1371/journal.pone.0072478
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