Antiproliferative Effects of Thymoquinone in MCF-7 Breast and HepG2 Liver Cancer Cells: Possible Role of Ceramide and ER Stress
- 16 March 2021
- journal article
- research article
- Published by Taylor & Francis Ltd in Nutrition and Cancer
- Vol. 73 (3), 460-472
- https://doi.org/10.1080/01635581.2020.1751216
Abstract
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 (NF kappa B1) and glucose-regulated protein 78-kd (GRP78) gene expressions were evaluated by quantitative PCR analysis, while NF-kappa B 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-kappa B1 mRNA and NF-kappa B 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-kappa B mediated cell survival may promote cancer cell death by triggering apoptosis.This publication has 34 references indexed in Scilit:
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