期刊
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
卷 73, 期 3, 页码 460-472出版社
ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
DOI: 10.1080/01635581.2020.1751216
关键词
-
资金
- Akdeniz University Research Foundation [TKA-2018-3876]
The study showed that treatment with thymoquinone (TQ) resulted in ceramide accumulation and endoplasmic reticulum stress in cancer cells, while decreasing S1P, C1P, and NF-kappa B mediated cell survival, ultimately promoting cancer cell death through apoptosis.
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.
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