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The Curcumin Analog (PAC) Suppressed Cell Survival and Induced Apoptosis and Autophagy in Oral Cancer Cells

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Journal Sci Rep
Specialty Science
Date 2021 Jun 4
PMID 34083581
Citations 24
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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 (p21) 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.

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References
1.
Alanazi H, Park H, Chakir J, Semlali A, Rouabhia M . Comparative study of the effects of cigarette smoke and electronic cigarettes on human gingival fibroblast proliferation, migration and apoptosis. Food Chem Toxicol. 2018; 118:390-398. DOI: 10.1016/j.fct.2018.05.049. View

2.
Semlali A, Witoled C, Alanazi M, Rouabhia M . Whole cigarette smoke increased the expression of TLRs, HBDs, and proinflammory cytokines by human gingival epithelial cells through different signaling pathways. PLoS One. 2013; 7(12):e52614. PMC: 3532503. DOI: 10.1371/journal.pone.0052614. View

3.
Schieke S, Ma M, Cao L, McCoy Jr J, Liu C, Hensel N . Mitochondrial metabolism modulates differentiation and teratoma formation capacity in mouse embryonic stem cells. J Biol Chem. 2008; 283(42):28506-12. PMC: 2568919. DOI: 10.1074/jbc.M802763200. View

4.
Mahmood K, Zia K, Zuber M, Salman M, Anjum M . Recent developments in curcumin and curcumin based polymeric materials for biomedical applications: A review. Int J Biol Macromol. 2015; 81:877-90. DOI: 10.1016/j.ijbiomac.2015.09.026. View

5.
Nazarewicz R, Dikalova A, Bikineyeva A, Ivanov S, Kirilyuk I, Grigorev I . Does scavenging of mitochondrial superoxide attenuate cancer prosurvival signaling pathways?. Antioxid Redox Signal. 2013; 19(4):344-9. PMC: 3700017. DOI: 10.1089/ars.2013.5185. View