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Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression, elevated levels of TRAIL receptors, oxidative stress and apoptosis
- Source :
- Molecular and Cellular Biochemistry. 389:85-98
- Publication Year :
- 2014
- Publisher :
- Springer Science and Business Media LLC, 2014.
-
Abstract
- Hepatocellular carcinoma (HCC) is the fourth most common solid tumor worldwide. The chemokine interleukin-8 (IL-8) is overexpressed in HCC and is a potential target for therapy. Although the transcription factor NF-κB regulates IL-8 expression, and while thymoquinone (TQ; the most bioactive constituent of black seed oil) inhibits NF-κB activity, the precise mechanisms by which TQ regulates IL-8 and cancer cell growth remain to be clarified. Here, we report that TQ inhibited growth of HCC cells in a dose- and time-dependent manner, caused G2M cell cycle arrest, and stimulated apoptosis. Apoptosis was substantiated by activation of caspase-3 and -9, as well as cleavage of poly(ADP-ribose)polymerase. TQ treatments inhibited expression of NF-κB and suppressed IL-8 and its receptors. TQ treatments caused increased levels of reactive oxygen species (ROS) and mRNAs of oxidative stress-related genes, NQO1 and HO-1. Pretreatment of HepG2 cells with N-acetylcysteine, a scavenger of ROS, prevented TQ-induced cell death. TQ treatment stimulated mRNA expression of pro-apoptotic Bcl-xS and TRAIL death receptors, and inhibited expression of the anti-apoptotic gene Bcl-2. TQ enhanced TRAIL-induced death of HepG2 cells, in part by up-regulating TRAIL death receptors, inhibiting NF-κB and IL-8 and stimulating apoptosis. Altogether, these findings provide insights into the pleiotropic molecular mechanisms of TQ-dependent suppression of HCC cell growth and underscore potential of this compound as anti-HCC drug.
- Subjects :
- Chemokine
Programmed cell death
Carcinoma, Hepatocellular
Clinical Biochemistry
bcl-X Protein
Apoptosis
chemistry.chemical_compound
Cell Line, Tumor
Benzoquinones
Humans
Interleukin 8
Receptor
Molecular Biology
Thymoquinone
Cell Proliferation
biology
Caspase 3
Cell growth
Interleukin-8
Liver Neoplasms
NF-kappa B
Hep G2 Cells
Cell Biology
General Medicine
Molecular biology
Caspase 9
G2 Phase Cell Cycle Checkpoints
Oxidative Stress
Receptors, TNF-Related Apoptosis-Inducing Ligand
Proto-Oncogene Proteins c-bcl-2
chemistry
Cancer cell
biology.protein
Cancer research
M Phase Cell Cycle Checkpoints
Poly(ADP-ribose) Polymerases
Reactive Oxygen Species
Subjects
Details
- ISSN :
- 15734919 and 03008177
- Volume :
- 389
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Biochemistry
- Accession number :
- edsair.doi.dedup.....2c68e66d99cd2932ba641c02534e8683