Antiproliferative Effects of Thymoquinone in MCF-7 Breast and HepG2 Liver Cancer Cells: Possible Role of Ceramide and ER Stress.

Autor:	Aslan, Mutay, Afşar, Ebru, Kırımlıoglu, Esma, Çeker, Tuğçe, Yılmaz, Çağatay
Předmět:	THERAPEUTIC use of antineoplastic agents PROTEIN metabolism GLUCOSE metabolism APOPTOSIS BREAST tumors CELL lines ENZYMES EPITHELIAL cells FLUORESCENT antibody technique GENE expression IMMUNOASSAY LIVER tumors MESSENGER RNA METABOLITES POLYMERASE chain reaction PROTEINS SPHINGOLIPIDS PSYCHOLOGICAL stress WESTERN immunoblotting DNA-binding proteins CERAMIDES QUANTITATIVE research BENZOQUINONES CELL survival
Zdroj:	Nutrition & Cancer; 2021, Vol. 73 Issue 3, p460-472, 13p, 2 Charts, 6 Graphs
Abstrakt:	We aimed to investigate the impact of thymoquinone (TQ), on sphingolipid metabolites, ER stress and apoptotic pathways in MCF-7 and HepG2 cancer cells. Antiproliferative effect was exerted in cancer cells via TQ incubation at different doses and durations. Cell viability was measured by MTT assay. Levels of sphingosine-1-phosphate (S1P), C16-C24 sphingomyelins (SM) and C16-C24 ceramides (CER) were determined by LC-MS/MS. Neutral sphingomyelinase (N-SMase) enzyme activity was measured by colorimetric assay and ceramide-1-phosphate (C1P) levels were determined by immunoassay. Nuclear factor kappa-b subunit 1 (NFκB1) and glucose-regulated protein 78-kd (GRP78) gene expressions were evaluated by quantitative PCR analysis, while NF-κB p65, GRP 78 and cleaved caspase-3 protein levels were assesed by immunofluorescence and western blot analysis. Incubation with TQ significantly decreased cell viability, S1P, C1P, NF-κB1 mRNA and NF-κB p65 protein levels in cancer cells compared to controls. A significant increase was observed in N-SMase activity, cellular levels of C16-C24 CERs and cleaved caspase-3 levels in cancer cells treated with TQ. GRP78 mRNA and protein levels also increased in cancer cells treated with TQ. In conclusion, TQ-induced ceramide accumulation and ER stress in conjunction with decreased S1P, C1P and NF-κB mediated cell survival may promote cancer cell death by triggering apoptosis. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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