Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression, elevated levels of TRAIL receptors, oxidative stress and apoptosis
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 constitu...
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| Format: | Article |
| Language: | English English |
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Springer US
2014
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| Online Access: | http://irep.iium.edu.my/63263/ http://irep.iium.edu.my/63263/1/8129_Thymoquinone%20suppression%20of%20the%20human.pdf http://irep.iium.edu.my/63263/2/8129_Thymoquinone%20suppression%20of%20the%20human_SCOPUS.pdf |
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| author | Ashour, Abdelkader Elbadawy Abbas Abd-Allah, Adel R. A. Korashy, Hesham M. Attia, Sabry M. Alzahrani, Abderlrahman Z. Saquib, Quaiser Bakheet, Saleh A. Abdel-Hamied, Hala E. |
| author_facet | Ashour, Abdelkader Elbadawy Abbas Abd-Allah, Adel R. A. Korashy, Hesham M. Attia, Sabry M. Alzahrani, Abderlrahman Z. Saquib, Quaiser Bakheet, Saleh A. Abdel-Hamied, Hala E. |
| author_sort | Ashour, Abdelkader Elbadawy Abbas |
| building | IIUM Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T17:02:07Z |
| format | Article |
| id | iium-63263 |
| institution | International Islamic University Malaysia |
| institution_category | Local University |
| language | English English |
| last_indexed | 2025-11-14T17:02:07Z |
| publishDate | 2014 |
| publisher | Springer US |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | iium-632632018-05-15T01:02:50Z http://irep.iium.edu.my/63263/ Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression, elevated levels of TRAIL receptors, oxidative stress and apoptosis Ashour, Abdelkader Elbadawy Abbas Abd-Allah, Adel R. A. Korashy, Hesham M. Attia, Sabry M. Alzahrani, Abderlrahman Z. Saquib, Quaiser Bakheet, Saleh A. Abdel-Hamied, Hala E. RM Therapeutics. Pharmacology 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. Springer US 2014-04-01 Article PeerReviewed application/pdf en http://irep.iium.edu.my/63263/1/8129_Thymoquinone%20suppression%20of%20the%20human.pdf application/pdf en http://irep.iium.edu.my/63263/2/8129_Thymoquinone%20suppression%20of%20the%20human_SCOPUS.pdf Ashour, Abdelkader Elbadawy Abbas and Abd-Allah, Adel R. A. and Korashy, Hesham M. and Attia, Sabry M. and Alzahrani, Abderlrahman Z. and Saquib, Quaiser and Bakheet, Saleh A. and Abdel-Hamied, Hala E. (2014) Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression, elevated levels of TRAIL receptors, oxidative stress and apoptosis. Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression, elevated levels of TRAIL receptors, oxidative stress and apoptosis, 389 (1-2). pp. 85-98. ISSN 0300-8177 E-ISSN 1573-4919 https://link.springer.com/article/10.1007%2Fs11010-013-1930-1 doi.org/10.1007/s11010-013-1930-1 |
| spellingShingle | RM Therapeutics. Pharmacology Ashour, Abdelkader Elbadawy Abbas Abd-Allah, Adel R. A. Korashy, Hesham M. Attia, Sabry M. Alzahrani, Abderlrahman Z. Saquib, Quaiser Bakheet, Saleh A. Abdel-Hamied, Hala E. Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression, elevated levels of TRAIL receptors, oxidative stress and apoptosis |
| title | Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression, elevated levels of TRAIL receptors, oxidative stress and apoptosis |
| title_full | Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression, elevated levels of TRAIL receptors, oxidative stress and apoptosis |
| title_fullStr | Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression, elevated levels of TRAIL receptors, oxidative stress and apoptosis |
| title_full_unstemmed | Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression, elevated levels of TRAIL receptors, oxidative stress and apoptosis |
| title_short | Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression, elevated levels of TRAIL receptors, oxidative stress and apoptosis |
| title_sort | thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of il-8 expression, elevated levels of trail receptors, oxidative stress and apoptosis |
| topic | RM Therapeutics. Pharmacology |
| url | http://irep.iium.edu.my/63263/ http://irep.iium.edu.my/63263/ http://irep.iium.edu.my/63263/ http://irep.iium.edu.my/63263/1/8129_Thymoquinone%20suppression%20of%20the%20human.pdf http://irep.iium.edu.my/63263/2/8129_Thymoquinone%20suppression%20of%20the%20human_SCOPUS.pdf |