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Characterization of Anti-Cancer Activities of Violacein: Actions on Tumor Cells and the Tumor Microenvironment

Natural products have been shown to serve as promising starting points for novel anti-cancer drugs. In this study, the anti-cancer activities of the purple compound violacein, initially isolated from Chromobacterium violaceum, were investigated. To highlight the crucial role of the tumor microenviro...

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Autores principales: Dahlem, Charlotte, Chanda, Shilpee, Hemmer, Jan, Schymik, Hanna S., Kohlstedt, Michael, Wittmann, Christoph, Kiemer, Alexandra K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130777/
https://www.ncbi.nlm.nih.gov/pubmed/35646663
http://dx.doi.org/10.3389/fonc.2022.872223
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author Dahlem, Charlotte
Chanda, Shilpee
Hemmer, Jan
Schymik, Hanna S.
Kohlstedt, Michael
Wittmann, Christoph
Kiemer, Alexandra K.
author_facet Dahlem, Charlotte
Chanda, Shilpee
Hemmer, Jan
Schymik, Hanna S.
Kohlstedt, Michael
Wittmann, Christoph
Kiemer, Alexandra K.
author_sort Dahlem, Charlotte
collection PubMed
description Natural products have been shown to serve as promising starting points for novel anti-cancer drugs. In this study, the anti-cancer activities of the purple compound violacein, initially isolated from Chromobacterium violaceum, were investigated. To highlight the crucial role of the tumor microenvironment on the effectiveness of cancer therapies, this study includes effects on macrophages as prototypic cells of the microenvironment in addition to the investigation of tumor-centric activities. Using 2D and 3D cell culture models, automated live-cell microscopy, and biochemical analyses, violacein was demonstrated to inhibit tumor cell proliferation and migration. The violacein-triggered tumor cell death was further associated with caspase 3-like activation and ATP release. Stimuli released from dead cells resulted in inflammatory activation of macrophages, as shown by NF-κB reporter cell assays, macrophage morphology, and gene expression analysis. Moreover, macrophages deficient in the inflammasome component Nlrp3 were found to be significantly less sensitive towards treatment with violacein and doxorubicin. Taken together, this study provides new insights into the biological activity of violacein against cancer. In addition, the in vitro data suggest immunogenic features of induced cell death, making violacein an interesting candidate for further studies investigating the compound as an inducer of immunogenic cell death.
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spelling pubmed-91307772022-05-26 Characterization of Anti-Cancer Activities of Violacein: Actions on Tumor Cells and the Tumor Microenvironment Dahlem, Charlotte Chanda, Shilpee Hemmer, Jan Schymik, Hanna S. Kohlstedt, Michael Wittmann, Christoph Kiemer, Alexandra K. Front Oncol Oncology Natural products have been shown to serve as promising starting points for novel anti-cancer drugs. In this study, the anti-cancer activities of the purple compound violacein, initially isolated from Chromobacterium violaceum, were investigated. To highlight the crucial role of the tumor microenvironment on the effectiveness of cancer therapies, this study includes effects on macrophages as prototypic cells of the microenvironment in addition to the investigation of tumor-centric activities. Using 2D and 3D cell culture models, automated live-cell microscopy, and biochemical analyses, violacein was demonstrated to inhibit tumor cell proliferation and migration. The violacein-triggered tumor cell death was further associated with caspase 3-like activation and ATP release. Stimuli released from dead cells resulted in inflammatory activation of macrophages, as shown by NF-κB reporter cell assays, macrophage morphology, and gene expression analysis. Moreover, macrophages deficient in the inflammasome component Nlrp3 were found to be significantly less sensitive towards treatment with violacein and doxorubicin. Taken together, this study provides new insights into the biological activity of violacein against cancer. In addition, the in vitro data suggest immunogenic features of induced cell death, making violacein an interesting candidate for further studies investigating the compound as an inducer of immunogenic cell death. Frontiers Media S.A. 2022-05-11 /pmc/articles/PMC9130777/ /pubmed/35646663 http://dx.doi.org/10.3389/fonc.2022.872223 Text en Copyright © 2022 Dahlem, Chanda, Hemmer, Schymik, Kohlstedt, Wittmann and Kiemer https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Dahlem, Charlotte
Chanda, Shilpee
Hemmer, Jan
Schymik, Hanna S.
Kohlstedt, Michael
Wittmann, Christoph
Kiemer, Alexandra K.
Characterization of Anti-Cancer Activities of Violacein: Actions on Tumor Cells and the Tumor Microenvironment
title Characterization of Anti-Cancer Activities of Violacein: Actions on Tumor Cells and the Tumor Microenvironment
title_full Characterization of Anti-Cancer Activities of Violacein: Actions on Tumor Cells and the Tumor Microenvironment
title_fullStr Characterization of Anti-Cancer Activities of Violacein: Actions on Tumor Cells and the Tumor Microenvironment
title_full_unstemmed Characterization of Anti-Cancer Activities of Violacein: Actions on Tumor Cells and the Tumor Microenvironment
title_short Characterization of Anti-Cancer Activities of Violacein: Actions on Tumor Cells and the Tumor Microenvironment
title_sort characterization of anti-cancer activities of violacein: actions on tumor cells and the tumor microenvironment
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130777/
https://www.ncbi.nlm.nih.gov/pubmed/35646663
http://dx.doi.org/10.3389/fonc.2022.872223
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