Thymoquinone suppresses growth and induces apoptosis via generation of reactive oxygen species in primary effusion lymphoma

Azhar R. Hussain, Maqbool Ahmed, Saeeda Ahmed, Pulicat Manogaran, Leonidas C. Platanias, Syed N. Alvi, Khawla S. Al-Kuraya, Shahab Uddin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

We provide evidence that thymoquinone (TQ), a natural compound isolated from Nigella sativa, induces growth inhibition and apoptosis in several primary effusion lymphoma (PEL) cell lines. Our data demonstrate that TQ treatment results in down-regulation of constitutive activation of AKT via generation of reactive oxygen species (ROS) and it causes conformational changes in Bax protein, leading to loss of mitochondrial membrane potential and release of cytochrome c to the cytosol. This leads to activation of caspase-9, caspase-3, and polyadenosine 5′-diphosphate ribose polymerase cleavage, leading to caspase-dependent apoptosis. Pretreatment of PEL cells with N-acetylcysteine, a scavenger of ROS, prevented TQ-mediated effects. In addition, subtoxic doses of TQ sensitized PEL cells to TRAIL via up-regulation of DR5. Altogether, these findings demonstrate that TQ is a potent inducer of apoptosis in PEL cells via release of ROS. They also raise the possibility that incorporation of TQ in treatment regimens for primary effusion lymphomas may provide a novel approach to sensitizing malignant cells and provide a molecular basis for such future translational efforts.

Original languageEnglish (US)
Pages (from-to)978-987
Number of pages10
JournalFree Radical Biology and Medicine
Volume50
Issue number8
DOIs
StatePublished - Apr 15 2011

Keywords

  • Cell death
  • Free radicals
  • NHL therapy
  • Primary effusion lymphoma
  • Thymoquinone

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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