The curcumin analog (PAC) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells
| Autor: | Fatiha Chandad, Camille Contant, Basem Al-Otaibi, Ibrahim Al-Jammaz, Abdelhabib Semlali |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell biology Programmed cell death Cell signaling Curcumin Cancer therapy Molecular biology Cell Survival p38 mitogen-activated protein kinases Science Apoptosis medicine.disease_cause Article 03 medical and health sciences Targeted therapies 0302 clinical medicine Autophagy medicine Humans Head and neck cancer Cancer Membrane Potential Mitochondrial Multidisciplinary Chemistry Cell growth Wnt signaling pathway 030104 developmental biology Head and Neck Neoplasms 030220 oncology & carcinogenesis Cancer cell Cancer research Medicine Mouth Neoplasms Plant sciences Oxidative stress Signal Transduction |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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