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Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in men and in women. The impact of the new pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide (MM-129) was evaluated against human colon cancer in vitro and in zebrafish xenografts. Our results show that this new sy...

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Autores principales: Hermanowicz, Justyna Magdalena, Szymanowska, Anna, Sieklucka, Beata, Czarnomysy, Robert, Pawlak, Krystyna, Bielawska, Anna, Bielawski, Krzysztof, Kalafut, Joanna, Przybyszewska, Alicja, Surazynski, Arkadiusz, Rivero-Muller, Adolfo, Mojzych, Mariusz, Pawlak, Dariusz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850456/
https://www.ncbi.nlm.nih.gov/pubmed/33522320
http://dx.doi.org/10.1080/14756366.2021.1879803
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author Hermanowicz, Justyna Magdalena
Szymanowska, Anna
Sieklucka, Beata
Czarnomysy, Robert
Pawlak, Krystyna
Bielawska, Anna
Bielawski, Krzysztof
Kalafut, Joanna
Przybyszewska, Alicja
Surazynski, Arkadiusz
Rivero-Muller, Adolfo
Mojzych, Mariusz
Pawlak, Dariusz
author_facet Hermanowicz, Justyna Magdalena
Szymanowska, Anna
Sieklucka, Beata
Czarnomysy, Robert
Pawlak, Krystyna
Bielawska, Anna
Bielawski, Krzysztof
Kalafut, Joanna
Przybyszewska, Alicja
Surazynski, Arkadiusz
Rivero-Muller, Adolfo
Mojzych, Mariusz
Pawlak, Dariusz
author_sort Hermanowicz, Justyna Magdalena
collection PubMed
description Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in men and in women. The impact of the new pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide (MM-129) was evaluated against human colon cancer in vitro and in zebrafish xenografts. Our results show that this new synthesised compound effectively inhibits cell survival in BTK-dependent mechanism. Its effectiveness is much higher at a relatively low concentration as compared with the standard chemotherapy used for CRC, i.e. 5-fluorouracil (5-FU). Flow cytometry analysis after annexin V-FITC and propidium iodide staining revealed that apoptosis was the main response of CRC cells to MM-129 treatment. We also found that MM-129 effectively inhibits tumour development in zebrafish embryo xenograft model, where it showed a markedly synergistic anticancer effect when used in combination with 5-FU. The above results suggest that this novel heterofused 1,2,4-triazine derivative may be a promising candidate for further evaluation as chemotherapeutic agent against CRC.
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spelling pubmed-78504562021-02-05 Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer Hermanowicz, Justyna Magdalena Szymanowska, Anna Sieklucka, Beata Czarnomysy, Robert Pawlak, Krystyna Bielawska, Anna Bielawski, Krzysztof Kalafut, Joanna Przybyszewska, Alicja Surazynski, Arkadiusz Rivero-Muller, Adolfo Mojzych, Mariusz Pawlak, Dariusz J Enzyme Inhib Med Chem Research Paper Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in men and in women. The impact of the new pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide (MM-129) was evaluated against human colon cancer in vitro and in zebrafish xenografts. Our results show that this new synthesised compound effectively inhibits cell survival in BTK-dependent mechanism. Its effectiveness is much higher at a relatively low concentration as compared with the standard chemotherapy used for CRC, i.e. 5-fluorouracil (5-FU). Flow cytometry analysis after annexin V-FITC and propidium iodide staining revealed that apoptosis was the main response of CRC cells to MM-129 treatment. We also found that MM-129 effectively inhibits tumour development in zebrafish embryo xenograft model, where it showed a markedly synergistic anticancer effect when used in combination with 5-FU. The above results suggest that this novel heterofused 1,2,4-triazine derivative may be a promising candidate for further evaluation as chemotherapeutic agent against CRC. Taylor & Francis 2021-01-31 /pmc/articles/PMC7850456/ /pubmed/33522320 http://dx.doi.org/10.1080/14756366.2021.1879803 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Hermanowicz, Justyna Magdalena
Szymanowska, Anna
Sieklucka, Beata
Czarnomysy, Robert
Pawlak, Krystyna
Bielawska, Anna
Bielawski, Krzysztof
Kalafut, Joanna
Przybyszewska, Alicja
Surazynski, Arkadiusz
Rivero-Muller, Adolfo
Mojzych, Mariusz
Pawlak, Dariusz
Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer
title Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer
title_full Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer
title_fullStr Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer
title_full_unstemmed Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer
title_short Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer
title_sort exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850456/
https://www.ncbi.nlm.nih.gov/pubmed/33522320
http://dx.doi.org/10.1080/14756366.2021.1879803
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