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The curcumin analog (PAC) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells
PAC (3,5-Bis (4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidone), a novel bioactive curcumin analog, has been reported to have anticancer properties against various tumors. However, the anti-cancer effects of PAC on oral cavity squamous cell carcinoma were not studied yet. Our aim is to investig...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175612/ https://www.ncbi.nlm.nih.gov/pubmed/34083581 http://dx.doi.org/10.1038/s41598-021-90754-x |
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author | Semlali, Abdelhabib Contant, Camille Al-Otaibi, Basem Al-Jammaz, Ibrahim Chandad, Fatiha |
author_facet | Semlali, Abdelhabib Contant, Camille Al-Otaibi, Basem Al-Jammaz, Ibrahim Chandad, Fatiha |
author_sort | Semlali, Abdelhabib |
collection | PubMed |
description | PAC (3,5-Bis (4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidone), a novel bioactive curcumin analog, has been reported to have anticancer properties against various tumors. However, the anti-cancer effects of PAC on oral cavity squamous cell carcinoma were not studied yet. Our aim is to investigate the anti-oral cancer properties of PAC in vitro, and determine the molecular mechanisms underlying these effects. Viability assays including MTT and LDH were conducted to measure cell proliferation. Flow cytometry-based cytotoxicity assay was performed to detect autophagic cell death and oxidative stress markers. Western blotting was used for measuring protein expression/activation in apoptotic, autophagic and pro-carcinogenic cellular signaling pathways. We demonstrated that PAC preferentially and, in a dose, -dependent way kills oral cancer cells, but was not toxic to normal human gingival cells. PAC destabilizes cell-cycle distributions, inhibits the expression of oncogenes (cyclin D1) and that of cyclin-dependent kinase inhibitor (p21(WAF1)) is upregulated, increases the expression of p53 gene, and inhibits epithelial-mesenchymal transition markers in oral cancer cells. The PAC effect involve various signaling pathways including NF-κB, MAPK, Wnt, caspase-3/9 and PARP1. Finally, PAC demonstrated ability to induce autophagy, decrease production of reactive oxygen species, increase intracellular glutathione (GSH) activity, and reduce mitochondrial membrane potential in oral cancer cells. In conclusion, PAC inhibits the proliferation and increases the apoptosis and autophagy and oxidative stress of oral cancer cells. These effects involve ERK1/2, p38/JNK, NF-κB and Wnt cellular signaling pathways. Overall, our study suggests the potential use of PAC to treat oral cancer. |
format | Online Article Text |
id | pubmed-8175612 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81756122021-06-07 The curcumin analog (PAC) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells Semlali, Abdelhabib Contant, Camille Al-Otaibi, Basem Al-Jammaz, Ibrahim Chandad, Fatiha Sci Rep Article PAC (3,5-Bis (4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidone), a novel bioactive curcumin analog, has been reported to have anticancer properties against various tumors. However, the anti-cancer effects of PAC on oral cavity squamous cell carcinoma were not studied yet. Our aim is to investigate the anti-oral cancer properties of PAC in vitro, and determine the molecular mechanisms underlying these effects. Viability assays including MTT and LDH were conducted to measure cell proliferation. Flow cytometry-based cytotoxicity assay was performed to detect autophagic cell death and oxidative stress markers. Western blotting was used for measuring protein expression/activation in apoptotic, autophagic and pro-carcinogenic cellular signaling pathways. We demonstrated that PAC preferentially and, in a dose, -dependent way kills oral cancer cells, but was not toxic to normal human gingival cells. PAC destabilizes cell-cycle distributions, inhibits the expression of oncogenes (cyclin D1) and that of cyclin-dependent kinase inhibitor (p21(WAF1)) is upregulated, increases the expression of p53 gene, and inhibits epithelial-mesenchymal transition markers in oral cancer cells. The PAC effect involve various signaling pathways including NF-κB, MAPK, Wnt, caspase-3/9 and PARP1. Finally, PAC demonstrated ability to induce autophagy, decrease production of reactive oxygen species, increase intracellular glutathione (GSH) activity, and reduce mitochondrial membrane potential in oral cancer cells. In conclusion, PAC inhibits the proliferation and increases the apoptosis and autophagy and oxidative stress of oral cancer cells. These effects involve ERK1/2, p38/JNK, NF-κB and Wnt cellular signaling pathways. Overall, our study suggests the potential use of PAC to treat oral cancer. Nature Publishing Group UK 2021-06-03 /pmc/articles/PMC8175612/ /pubmed/34083581 http://dx.doi.org/10.1038/s41598-021-90754-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Semlali, Abdelhabib Contant, Camille Al-Otaibi, Basem Al-Jammaz, Ibrahim Chandad, Fatiha The curcumin analog (PAC) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells |
title | The curcumin analog (PAC) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells |
title_full | The curcumin analog (PAC) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells |
title_fullStr | The curcumin analog (PAC) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells |
title_full_unstemmed | The curcumin analog (PAC) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells |
title_short | The curcumin analog (PAC) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells |
title_sort | curcumin analog (pac) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175612/ https://www.ncbi.nlm.nih.gov/pubmed/34083581 http://dx.doi.org/10.1038/s41598-021-90754-x |
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