Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-jB signaling and IL-8 expression
Medulloblastoma (MB) is the most common malignant brain tumor of childhood. The transcription factor NF-κB is overexpressed in human MB and is a critical factor for MB tumor growth. NF-κB is known to regulate the expression of interleukin-8 (IL-8), the chemokine that enhances cancer cell growth and...
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Springer US
2016
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| Online Access: | http://irep.iium.edu.my/59658/ http://irep.iium.edu.my/59658/1/Thymoquinone%20inhibits%20growth%20of%20human%20medulloblastoma%20cells%20by%20inducing%20oxidative%20stress%20and%20caspase-dependent%20apoptosis%20while%20suppressing%20NF-%CE%BAB%20signaling%20and%20IL-8%20expression.pdf http://irep.iium.edu.my/59658/7/59658_Thymoquinone%20inhibits%20growth%20of%20human_SCOPUS.pdf |
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| author | Ashour, Abdelkader Elbadawy Abbas Ahmed, Atallah F. Kumar, Ashok Zoheir, Khairy M. A. Aboul-Soud, Mourad A. Ahmad, Sheikh F. Attia, Sabry M. Abd-Allah, Adel R. A. Cheryan, Vino T. Rishi, Arun K. |
| author_facet | Ashour, Abdelkader Elbadawy Abbas Ahmed, Atallah F. Kumar, Ashok Zoheir, Khairy M. A. Aboul-Soud, Mourad A. Ahmad, Sheikh F. Attia, Sabry M. Abd-Allah, Adel R. A. Cheryan, Vino T. Rishi, Arun K. |
| author_sort | Ashour, Abdelkader Elbadawy Abbas |
| building | IIUM Repository |
| collection | Online Access |
| description | Medulloblastoma (MB) is the most common malignant brain tumor of childhood. The transcription factor NF-κB is overexpressed in human MB and is a critical factor for MB tumor growth. NF-κB is known to regulate the expression of interleukin-8 (IL-8), the chemokine that enhances cancer cell growth and resistance to chemotherapy. We have recently shown that thymoquinone (TQ) suppresses growth of hepatocellular carcinoma cells in part by inhibiting NF-κB signaling. Here we sought to extend these studies in MB cells and show that TQ suppresses growth of MB cells in a dose- and time-dependent manner, causes G2M cell cycle arrest, and induces apoptosis. TQ significantly increased generation of reactive oxygen species (ROS), while pretreatment of MB cells with the ROS scavenger N-acetylcysteine (NAC) abrogated TQ-induced cell death and apoptosis, suggesting that TQ-induced cell death and apoptosis are oxidative stress-mediated. TQ inhibitory effects were associated with inhibition of NF-κB and altered expression of its downstream effectors IL-8 and its receptors, the anti-apoptotic Bcl-2, Bcl-xL, X-IAP, and FLIP, as well as the pro-apoptotic TRAIL-R1, caspase-8, caspase-9, Bcl-xS, and cytochrome c. TQ-triggered apoptosis was substantiated by up-regulation of the executioner caspase-3 and caspase-7, as well as cleavage of the death substrate poly(ADP-ribose)polymerase. Interestingly, pretreatment of MB cells with NAC or the pan-caspase inhibitor zVAD-fmk abrogated TQ-induced apoptosis, loss of cyclin B1 and NF-κB activity, suggesting that these TQ-mediated effects are oxidative stress- and caspase-dependent. These findings reveal that TQ induces both extrinsic and intrinsic pathways of apoptosis in MB cells, and suggest its potential usefulness in the treatment of MB. |
| first_indexed | 2025-11-14T16:51:43Z |
| format | Article |
| id | iium-59658 |
| institution | International Islamic University Malaysia |
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| language | English English |
| last_indexed | 2025-11-14T16:51:43Z |
| publishDate | 2016 |
| publisher | Springer US |
| recordtype | eprints |
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| spelling | iium-596582017-11-29T06:37:46Z http://irep.iium.edu.my/59658/ Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-jB signaling and IL-8 expression Ashour, Abdelkader Elbadawy Abbas Ahmed, Atallah F. Kumar, Ashok Zoheir, Khairy M. A. Aboul-Soud, Mourad A. Ahmad, Sheikh F. Attia, Sabry M. Abd-Allah, Adel R. A. Cheryan, Vino T. Rishi, Arun K. RM Therapeutics. Pharmacology Medulloblastoma (MB) is the most common malignant brain tumor of childhood. The transcription factor NF-κB is overexpressed in human MB and is a critical factor for MB tumor growth. NF-κB is known to regulate the expression of interleukin-8 (IL-8), the chemokine that enhances cancer cell growth and resistance to chemotherapy. We have recently shown that thymoquinone (TQ) suppresses growth of hepatocellular carcinoma cells in part by inhibiting NF-κB signaling. Here we sought to extend these studies in MB cells and show that TQ suppresses growth of MB cells in a dose- and time-dependent manner, causes G2M cell cycle arrest, and induces apoptosis. TQ significantly increased generation of reactive oxygen species (ROS), while pretreatment of MB cells with the ROS scavenger N-acetylcysteine (NAC) abrogated TQ-induced cell death and apoptosis, suggesting that TQ-induced cell death and apoptosis are oxidative stress-mediated. TQ inhibitory effects were associated with inhibition of NF-κB and altered expression of its downstream effectors IL-8 and its receptors, the anti-apoptotic Bcl-2, Bcl-xL, X-IAP, and FLIP, as well as the pro-apoptotic TRAIL-R1, caspase-8, caspase-9, Bcl-xS, and cytochrome c. TQ-triggered apoptosis was substantiated by up-regulation of the executioner caspase-3 and caspase-7, as well as cleavage of the death substrate poly(ADP-ribose)polymerase. Interestingly, pretreatment of MB cells with NAC or the pan-caspase inhibitor zVAD-fmk abrogated TQ-induced apoptosis, loss of cyclin B1 and NF-κB activity, suggesting that these TQ-mediated effects are oxidative stress- and caspase-dependent. These findings reveal that TQ induces both extrinsic and intrinsic pathways of apoptosis in MB cells, and suggest its potential usefulness in the treatment of MB. Springer US 2016-05-01 Article PeerReviewed application/pdf en http://irep.iium.edu.my/59658/1/Thymoquinone%20inhibits%20growth%20of%20human%20medulloblastoma%20cells%20by%20inducing%20oxidative%20stress%20and%20caspase-dependent%20apoptosis%20while%20suppressing%20NF-%CE%BAB%20signaling%20and%20IL-8%20expression.pdf application/pdf en http://irep.iium.edu.my/59658/7/59658_Thymoquinone%20inhibits%20growth%20of%20human_SCOPUS.pdf Ashour, Abdelkader Elbadawy Abbas and Ahmed, Atallah F. and Kumar, Ashok and Zoheir, Khairy M. A. and Aboul-Soud, Mourad A. and Ahmad, Sheikh F. and Attia, Sabry M. and Abd-Allah, Adel R. A. and Cheryan, Vino T. and Rishi, Arun K. (2016) Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-jB signaling and IL-8 expression. Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-jB signaling and IL-8 expression, 416 ((1-2)). pp. 141-155. ISSN 0300-8177 E-ISSN 1573-4919 https://www.springer.com/life+sciences/biochemistry+%26+biophysics/journal/11010 10.1007/s11010-016-2703-4 |
| spellingShingle | RM Therapeutics. Pharmacology Ashour, Abdelkader Elbadawy Abbas Ahmed, Atallah F. Kumar, Ashok Zoheir, Khairy M. A. Aboul-Soud, Mourad A. Ahmad, Sheikh F. Attia, Sabry M. Abd-Allah, Adel R. A. Cheryan, Vino T. Rishi, Arun K. Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-jB signaling and IL-8 expression |
| title | Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-jB signaling and IL-8 expression |
| title_full | Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-jB signaling and IL-8 expression |
| title_fullStr | Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-jB signaling and IL-8 expression |
| title_full_unstemmed | Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-jB signaling and IL-8 expression |
| title_short | Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-jB signaling and IL-8 expression |
| title_sort | thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing nf-jb signaling and il-8 expression |
| topic | RM Therapeutics. Pharmacology |
| url | http://irep.iium.edu.my/59658/ http://irep.iium.edu.my/59658/ http://irep.iium.edu.my/59658/ http://irep.iium.edu.my/59658/1/Thymoquinone%20inhibits%20growth%20of%20human%20medulloblastoma%20cells%20by%20inducing%20oxidative%20stress%20and%20caspase-dependent%20apoptosis%20while%20suppressing%20NF-%CE%BAB%20signaling%20and%20IL-8%20expression.pdf http://irep.iium.edu.my/59658/7/59658_Thymoquinone%20inhibits%20growth%20of%20human_SCOPUS.pdf |