Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism

  • Authors:
    • Hala Gali-Muhtasib
    • Mona Diab-Assaf
    • Carsten Boltze
    • Josianne Al-Hmaira
    • Roland Hartig
    • Albert Roessner
    • Regine Schneider-Stock
  • View Affiliations

  • Published online on: Friday, October 1, 2004
  • Pages: 857-866
  • DOI: 10.3892/ijo.25.4.857

Abstract

For centuries, the black seed (Nigella sativa) herb and oil have been used in Asia, Middle East and Africa to promote health and fight disease. Thymoquinone (TQ), the most abundant constituent present in black seed, is a promising dietary chemopreventive agent. We investigated the effects of thymoquinone (TQ) against HCT-116 human colon cancer cells and attempted to identify its potential molecular mechanisms of action. We report that TQ inhibits the growth of colon cancer cells which was correlated with G1 phase arrest of the cell cycle. Furthermore, TUNEL staining and flow cytometry analysis indicate that TQ triggers apoptosis in a dose- and time-dependent manner. Apoptosis induction by TQ was associated with a 2.5-4.5-fold increase in mRNA expression of p53 and the downstream p53 target gene, p21WAF1. Simultaneously, we found a marked increase in p53 and p21WAF1 protein levels but a significant inhibition of anti-apoptotic Bcl-2 protein. Co-incubation with pifithrin-α (PFT-α), a specific inhibitor of p53, restored Bcl-2, p53 and p21WAF1 levels to the untreated control and suppressed TQ-induced cell cycle arrest and apoptosis. p53-null HCT-116 cells were less sensitive to TQ-induced growth arrest and apoptosis. These results indicate that TQ is antineoplastic and pro-apoptotic against colon cancer cell line HCT116. The apoptotic effects of TQ are modulated by Bcl-2 protein and are linked to and dependent on p53. Our data support the potential for using the agent TQ for the treatment of colon cancer.
Journal Cover

October 2004
Volume 25 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
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APA
Gali-Muhtasib, H., Diab-Assaf, M., Boltze, C., Al-Hmaira, J., Hartig, R., Roessner, A., & Schneider-Stock, R. (2004). Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism. International Journal of Oncology, 25(4), 857-866.
MLA
Gali-Muhtasib, Diab-Assaf, Boltze, Al-Hmaira, Hartig, Roessner, and Regine Schneider-Stock. "Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism." International Journal of Oncology International Journal of Oncology 25.4 (2004): 857-866.
Chicago
Gali-Muhtasib, Diab-Assaf, Boltze, Al-Hmaira, Hartig, Roessner, and Regine Schneider-Stock. "Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism." International Journal of Oncology International Journal of Oncology 25 no. 4 (2004): 857-866.