Targeting lysosomes in colorectal cancer: exploring the anticancer activity of a new benzo[a]phenoxazine derivative
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/1822/84632 |
Resumo: | Colorectal cancer (CRC) has been ranked as one of the cancer types with a higher incidence and one of the most mortal. There are limited therapies available for CRC, which urges the finding of intracellular targets and the discovery of new drugs for innovative therapeutic approaches. In addition to the limited number of effective anticancer agents approved for use in humans, CRC resistance and secondary effects stemming from classical chemotherapy remain a major clinical problem, reinforcing the need for the development of novel drugs. In the recent years, the phenoxazines derivatives, Nile Blue analogues, have been shown to possess anticancer activity, which has created interest in exploring the potential of these compounds as anticancer drugs. In this context, we have synthetized and evaluated the anticancer activity of different benzo[<i>a</i>]phenoxazine derivatives for CRC therapy. Our results revealed that one particular compound, BaP1, displayed promising anticancer activity against CRC cells. We found that BaP1 is selective for CRC cells and reduces cell proliferation, cell survival, and cell migration. We observed that the compound is associated with reactive oxygen species (ROS) generation, accumulates in the lysosomes, and leads to lysosomal membrane permeabilization, cytosolic acidification, and apoptotic cell death. <i>In vivo</i> results using a chicken embryo choriollantoic membrane (CAM) assay showed that BaP1 inhibits tumor growth, angiogenesis, and tumor proliferation. These observations highlight that BaP1 as a very interesting agent to disturb and counteract the important roles of lysosomes in cancer and suggests BaP1 as a promising candidate to be exploited as new anticancer lysosomal-targeted agent, which uses lysosome membrane permeabilization (LMP) as a therapeutic approach in CRC. |
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Targeting lysosomes in colorectal cancer: exploring the anticancer activity of a new benzo[a]phenoxazine derivativeNile Blue analogueBenzo[a]phenoxazineAnticancer drugColorectal cancerLysosome membrane permeabilizationScience & TechnologyColorectal cancer (CRC) has been ranked as one of the cancer types with a higher incidence and one of the most mortal. There are limited therapies available for CRC, which urges the finding of intracellular targets and the discovery of new drugs for innovative therapeutic approaches. In addition to the limited number of effective anticancer agents approved for use in humans, CRC resistance and secondary effects stemming from classical chemotherapy remain a major clinical problem, reinforcing the need for the development of novel drugs. In the recent years, the phenoxazines derivatives, Nile Blue analogues, have been shown to possess anticancer activity, which has created interest in exploring the potential of these compounds as anticancer drugs. In this context, we have synthetized and evaluated the anticancer activity of different benzo[<i>a</i>]phenoxazine derivatives for CRC therapy. Our results revealed that one particular compound, BaP1, displayed promising anticancer activity against CRC cells. We found that BaP1 is selective for CRC cells and reduces cell proliferation, cell survival, and cell migration. We observed that the compound is associated with reactive oxygen species (ROS) generation, accumulates in the lysosomes, and leads to lysosomal membrane permeabilization, cytosolic acidification, and apoptotic cell death. <i>In vivo</i> results using a chicken embryo choriollantoic membrane (CAM) assay showed that BaP1 inhibits tumor growth, angiogenesis, and tumor proliferation. These observations highlight that BaP1 as a very interesting agent to disturb and counteract the important roles of lysosomes in cancer and suggests BaP1 as a promising candidate to be exploited as new anticancer lysosomal-targeted agent, which uses lysosome membrane permeabilization (LMP) as a therapeutic approach in CRC.Doctoral Grant J. Canossa Ferreira (SFRH/BD/133207/2017 and COVID/BD/151978/2021) acknowledged to (Fundação para a Ciência e Tecnologia) FCT. This work was supported by the strategic programs UID/BIA/04050/2020, UID/QUI/00686/2016, and UID/QUI/0686/2020 funded by national funds through the FCT I.P. The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased within the framework of the National Program for Scientific Re-equipment, contract REDE/1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT. This work was also funded by FCT within the scope of project PTDC/QUIQIN/28662/2017Multidisciplinary Digital Publishing Institute (MDPI)Universidade do MinhoFerreira, João C. C.Granja, Sara CostaAlmeida, Ana F.Baltazar, FátimaGonçalves, M. Sameiro T.Preto, AnaSousa, Maria João20232023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/84632engFerreira, J.C.C.; Granja, S.; Almeida, A.F.; Baltazar, F.; Gonçalves, M.S.T.; Preto, A.; Sousa, M.J. Targeting Lysosomes in Colorectal Cancer: Exploring the Anticancer Activity of a New Benzo[a]phenoxazine Derivative. Int. J. Mol. Sci. 2023, 24, 614. https://doi.org/10.3390/ijms240106141661-65961422-006710.3390/ijms2401061436614056614https://www.mdpi.com/1422-0067/24/1/614info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-12-23T01:27:42Zoai:repositorium.sdum.uminho.pt:1822/84632Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:49:17.860756Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Targeting lysosomes in colorectal cancer: exploring the anticancer activity of a new benzo[a]phenoxazine derivative |
title |
Targeting lysosomes in colorectal cancer: exploring the anticancer activity of a new benzo[a]phenoxazine derivative |
spellingShingle |
Targeting lysosomes in colorectal cancer: exploring the anticancer activity of a new benzo[a]phenoxazine derivative Ferreira, João C. C. Nile Blue analogue Benzo[a]phenoxazine Anticancer drug Colorectal cancer Lysosome membrane permeabilization Science & Technology |
title_short |
Targeting lysosomes in colorectal cancer: exploring the anticancer activity of a new benzo[a]phenoxazine derivative |
title_full |
Targeting lysosomes in colorectal cancer: exploring the anticancer activity of a new benzo[a]phenoxazine derivative |
title_fullStr |
Targeting lysosomes in colorectal cancer: exploring the anticancer activity of a new benzo[a]phenoxazine derivative |
title_full_unstemmed |
Targeting lysosomes in colorectal cancer: exploring the anticancer activity of a new benzo[a]phenoxazine derivative |
title_sort |
Targeting lysosomes in colorectal cancer: exploring the anticancer activity of a new benzo[a]phenoxazine derivative |
author |
Ferreira, João C. C. |
author_facet |
Ferreira, João C. C. Granja, Sara Costa Almeida, Ana F. Baltazar, Fátima Gonçalves, M. Sameiro T. Preto, Ana Sousa, Maria João |
author_role |
author |
author2 |
Granja, Sara Costa Almeida, Ana F. Baltazar, Fátima Gonçalves, M. Sameiro T. Preto, Ana Sousa, Maria João |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Ferreira, João C. C. Granja, Sara Costa Almeida, Ana F. Baltazar, Fátima Gonçalves, M. Sameiro T. Preto, Ana Sousa, Maria João |
dc.subject.por.fl_str_mv |
Nile Blue analogue Benzo[a]phenoxazine Anticancer drug Colorectal cancer Lysosome membrane permeabilization Science & Technology |
topic |
Nile Blue analogue Benzo[a]phenoxazine Anticancer drug Colorectal cancer Lysosome membrane permeabilization Science & Technology |
description |
Colorectal cancer (CRC) has been ranked as one of the cancer types with a higher incidence and one of the most mortal. There are limited therapies available for CRC, which urges the finding of intracellular targets and the discovery of new drugs for innovative therapeutic approaches. In addition to the limited number of effective anticancer agents approved for use in humans, CRC resistance and secondary effects stemming from classical chemotherapy remain a major clinical problem, reinforcing the need for the development of novel drugs. In the recent years, the phenoxazines derivatives, Nile Blue analogues, have been shown to possess anticancer activity, which has created interest in exploring the potential of these compounds as anticancer drugs. In this context, we have synthetized and evaluated the anticancer activity of different benzo[<i>a</i>]phenoxazine derivatives for CRC therapy. Our results revealed that one particular compound, BaP1, displayed promising anticancer activity against CRC cells. We found that BaP1 is selective for CRC cells and reduces cell proliferation, cell survival, and cell migration. We observed that the compound is associated with reactive oxygen species (ROS) generation, accumulates in the lysosomes, and leads to lysosomal membrane permeabilization, cytosolic acidification, and apoptotic cell death. <i>In vivo</i> results using a chicken embryo choriollantoic membrane (CAM) assay showed that BaP1 inhibits tumor growth, angiogenesis, and tumor proliferation. These observations highlight that BaP1 as a very interesting agent to disturb and counteract the important roles of lysosomes in cancer and suggests BaP1 as a promising candidate to be exploited as new anticancer lysosomal-targeted agent, which uses lysosome membrane permeabilization (LMP) as a therapeutic approach in CRC. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023 2023-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/1822/84632 |
url |
https://hdl.handle.net/1822/84632 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Ferreira, J.C.C.; Granja, S.; Almeida, A.F.; Baltazar, F.; Gonçalves, M.S.T.; Preto, A.; Sousa, M.J. Targeting Lysosomes in Colorectal Cancer: Exploring the Anticancer Activity of a New Benzo[a]phenoxazine Derivative. Int. J. Mol. Sci. 2023, 24, 614. https://doi.org/10.3390/ijms24010614 1661-6596 1422-0067 10.3390/ijms24010614 36614056 614 https://www.mdpi.com/1422-0067/24/1/614 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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