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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Main Authors:	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.
Format:	Article
Language:	English English
Published:	Springer US 2016
Subjects:	RM Therapeutics. Pharmacology
Online Access:	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

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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
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English
topic	RM Therapeutics. Pharmacology
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
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.
format	Article
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
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_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_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_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
publisher	Springer US
publishDate	2016
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
first_indexed	2023-09-18T21:24:31Z
last_indexed	2023-09-18T21:24:31Z
_version_	1777412102486491136

Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-jB signaling and IL-8 expression

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