Dr. Weeks’ Comment: Thymoquinone, a key ingredient in SOUL (the 3 seed drink made from anti-inflammatory seeds) is a powerful agent for fighting against lymphoma.
Thymoquinone suppresses growth and induces apoptosis via generation of reactive oxygen species in primary effusion lymphoma
Free Radic. Biol. Med. (2011), doi:10.1016/j.freeradbiomed.2010.12.034
Azhar R. Hussain a, Maqbool Ahmed a, Saeeda Ahmed a, Pulicat Manogaran b, Leonidas C. Platanias c, Syed N. Alvi d, Khawla S. Al-Kuraya a, Shahab Uddin a,âŽ
Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
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”²-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…
DISCUSSION
Induction of apoptosis in malignant cells is a very important mechanism of action of some chemopreventive agents [43]. Thymoquinone, an active constituent of black seed, has well-documented proapoptotic properties in a variety of cell types, including cells of hematopoietic origin [17-20]. Previous studies have demonstrated that TQ induces apoptosis in various cancer cell types [44,45]. We now provide evidence that TQ induces cell death and apoptosis in PEL cell lines in a dose-dependent manner. We found that all PEL cell lines studied express constitutively phosphorylated/activated AKT and its downstreamtarget molecules, FOXO1, GSK3, and Bad. TQ treatment of PEL cell lines suppressed p-AKT in all cell lines via generation of ROS, and pretreatment of cells with NAC, a scavenger of ROS, abrogated the TQ-induced suppression of p-AKT. Furthermore, TQ-mediated ROS induced apoptosis occurred via modulation of Bax, suggesting that Bax plays a critical role in TQ-induced apoptosis….
Clinically, resistance to apoptosis by chemotherapeutic agents is a frequent problem that emerges during the management of malignancies.
The cytotoxic inducing ability of TQ in cancer could make it a potentially effective chemopreventive and/or therapeutic agent for the treatment of various tumors. Furthermore, the combination of subtoxic doses of TQ and TRAIL resulted in considerable apoptosis in PEL cells. PEL is a very aggressive lymphoma; thus, it is possible that combinations of TQ with chemotherapeutic agents may provide a novel therapeutic approach to sensitize these cells and increase clinical response. Based on our data, studies in that direction are
Supplementary materials related to this article can be found online
at doi:10.1016/j.freeradbiomed.2010.12.034.