The curcumin analog (PAC) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells

Abstract 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...

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Autores principales:	Abdelhabib Semlali, Camille Contant, Basem Al-Otaibi, Ibrahim Al-Jammaz, Fatiha Chandad
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3d7e5b83d5154a1d9bedd6eb63fbd80f
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spelling	oai:doaj.org-article:3d7e5b83d5154a1d9bedd6eb63fbd80f2021-12-02T18:25:05ZThe curcumin analog (PAC) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells10.1038/s41598-021-90754-x2045-2322https://doaj.org/article/3d7e5b83d5154a1d9bedd6eb63fbd80f2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90754-xhttps://doaj.org/toc/2045-2322Abstract 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 (p21WAF1) 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.Abdelhabib SemlaliCamille ContantBasem Al-OtaibiIbrahim Al-JammazFatiha ChandadNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Abdelhabib Semlali Camille Contant Basem Al-Otaibi Ibrahim Al-Jammaz Fatiha Chandad The curcumin analog (PAC) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells
description	Abstract 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 (p21WAF1) 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	article
author	Abdelhabib Semlali Camille Contant Basem Al-Otaibi Ibrahim Al-Jammaz Fatiha Chandad
author_facet	Abdelhabib Semlali Camille Contant Basem Al-Otaibi Ibrahim Al-Jammaz Fatiha Chandad
author_sort	Abdelhabib Semlali
title	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_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_sort	curcumin analog (pac) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3d7e5b83d5154a1d9bedd6eb63fbd80f
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The curcumin analog (PAC) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells

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