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

Research output: Contribution to journalArticle

25 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

Fingerprint

T-cells
Human T-lymphotropic virus 1
Reactive Oxygen Species
Apoptosis
T-Lymphocytes
Glutathione
Acetylcysteine
Adult T Cell Leukemia Lymphoma
Caspase 9
T-Cell Lymphoma
Mitochondrial Membrane Potential
Cell death
Blister
Caspases
Cytochromes c
Caspase 3
Catalase
Cysteine
Blood Cells
Leukemia

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., ... 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.

Thymoquinone induces apoptosis in malignant T-cells via generation of ROS. / Dergarabetian, Eileen Manasse; Ghattass, Khaled Imad; El-Sitt, Sally Boulos; Al Mismar, Rasha; El-Baba, Chirine Omar; Itani, Wafica Sami; Melhem, Nada Mohamad; El-Hajj, Hiba Ahmad; Bazarbachi, Ali Abdul Hamid; Schneider-Stock, Regine; Gali-Muhtasib, Hala Uthman.

In: Frontiers in Bioscience - Elite, Vol. 5 E, No. 2, 01.01.2013, p. 706-719.

Research output: Contribution to journalArticle

Dergarabetian, EM, Ghattass, KI, El-Sitt, SB, Al Mismar, R, El-Baba, CO, Itani, WS, Melhem, NM, El-Hajj, HA, Bazarbachi, AAH, Schneider-Stock, R & Gali-Muhtasib, HU 2013, 'Thymoquinone induces apoptosis in malignant T-cells via generation of ROS', Frontiers in Bioscience - Elite, vol. 5 E, no. 2, pp. 706-719.
Dergarabetian EM, Ghattass KI, El-Sitt SB, Al Mismar R, El-Baba CO, Itani WS et al. Thymoquinone induces apoptosis in malignant T-cells via generation of ROS. Frontiers in Bioscience - Elite. 2013 Jan 1;5 E(2):706-719.
Dergarabetian, Eileen Manasse ; Ghattass, Khaled Imad ; El-Sitt, Sally Boulos ; Al Mismar, Rasha ; El-Baba, Chirine Omar ; Itani, Wafica Sami ; Melhem, Nada Mohamad ; El-Hajj, Hiba Ahmad ; Bazarbachi, Ali Abdul Hamid ; Schneider-Stock, Regine ; Gali-Muhtasib, Hala Uthman. / Thymoquinone induces apoptosis in malignant T-cells via generation of ROS. In: Frontiers in Bioscience - Elite. 2013 ; Vol. 5 E, No. 2. pp. 706-719.
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