Thymoquinone induces apoptosis in malignant T-cells via generation of ROS

Eileen Manasse Dergarabetian, Khaled Imad Ghattass, Sally Boulos El-Sitt, Rasha Al Mismar, Chirine Omar El-Baba, Wafica Sami Itani, Nada Mohamad Melhem, Hiba Ahmad El-Hajj, Ali Abdul Hamid Bazarbachi, Regine Schneider-Stock, Hala Uthman Gali-Muhtasib

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26 Citations (Scopus)

Abstract

We show that HTLV-1 negative leukemia cells are more sensitive to TQ due to higher levels of drug-induced reactive oxygen species (ROS). PreG1 population in HTLV-1 negative Jurkat and CEM was higher than HTLV-1 transformed HuT-102 and MT-2 cells. Peripheral blood mononuclear cells were more resistant. Hoechst staining indicated more features of apoptosis, namely nuclear blebs and shrunken nuclei in HuT-102 than Jurkat. A greater depletion of the antioxidant enzyme glutathione occurred in Jurkat, which consequently led to an increase in ROS, loss of mitochondrial membrane potential, cytochrome c release, activation of caspases 3 and 9, and cleavage of PARP. Treatment with z- VAD-fmk partially reversed TQ-induced apoptosis, suggesting a caspase-dependent mechanism. N-acetyl cysteine prevented apoptosis providing evidence that cell death is ROSdependent. Catalase prevented apoptosis to a lesser extent than NAC. In summary, TQ induces apoptosis in adult T cell leukemia/lymphoma by decreasing glutathione and increasing ROS, and levels of ROS underlie the differential cellular response to TQ. Our data suggest a potential therapeutic role for TQ in sensitizing HTLV-I-negative T-cell lymphomas.

Original languageEnglish
Pages (from-to)706-719
Number of pages14
JournalFrontiers in Bioscience - Elite
Volume5 E
Issue number2
Publication statusPublished - 1 Jan 2013
Externally publishedYes

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Keywords

  • Anticancer
  • Apoptosis
  • ROS
  • T-cell leukemia
  • Thymoquinone

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)

Cite this

Dergarabetian, E. M., Ghattass, K. I., El-Sitt, S. B., Al Mismar, R., El-Baba, C. O., Itani, W. S., Melhem, N. M., El-Hajj, H. A., Bazarbachi, A. A. H., Schneider-Stock, R., & Gali-Muhtasib, H. U. (2013). Thymoquinone induces apoptosis in malignant T-cells via generation of ROS. Frontiers in Bioscience - Elite, 5 E(2), 706-719.