Anti-neoplastic agent thymoquinone induces degradation of α and β tubulin proteins in human cancer cells without affecting their level in normal human fibroblasts

Abstract

The microtubule-targeting agents derived from natural products, such as vinca-alkaloids and taxanes are an important family of efficient anti-cancer drugs with therapeutic benefits in both haematological and solid tumors. These drugs interfere with the assembly of microtubules of α/β tubulin heterodimers without altering their expression level. The aim of the present study was to investigate the effect of thymoquinone (TQ), a natural product present in black cumin seed oil known to exhibit putative anti-cancer activities, on α/β tubulin expression in human astrocytoma cells (cell line U87, solid tumor model) and in Jurkat cells (T lymphoblastic leukaemia cells). TQ induced a concentration- and time-dependent degradation of α/β tubulin in both cancer cell types. This degradation was associated with the up-regulation of the tumor suppressor p73 with subsequent induction of apoptosis. Interestingly, TQ had no effect on α/β tubulin protein expression in normal human fibroblast cells, which were used as a non-cancerous cell model. These data indicate that TQ exerts a selective effect towards α/β tubulin in cancer cells. In conclusion, the present findings indicate that TQ is a novel anti-microtubule drug which targets the level of α/β tubulin proteins in cancer cells. Furthermore, they highlight the interest of developing anti-cancer therapies that target directly tubulin rather than microtubules dynamics.

Thymoquinone Inhibits Autophagy and Induces Cathepsin-Mediated, Caspase-Independent Cell Death in Glioblastoma Cells

“…We also found that growth of normal human astrocytes is not affected by concentrations of TQ that are cytotoxic to glioblastoma cells. This is in agreement with previous reports showing that TQ is selective for cancer cells [24], [25], [54]. It is important to note that TQ readily crosses the blood brain barrier: in mouse models of petit mal epilepsy, TQ administered by intraperitoneal injection was shown to delay the onset and decrease the duration of seizures [26], and in rat models of ischemia-induced brain injury, TQ administered in drinking water prevented the depletion of several crucial endogenous neuronal antioxidants [27].…”

“…It is known that microtubule poisons, such as paclitaxel and vincristine, are capable of inducing LMP [38], [44], [57] and interfering with lysosomal trafficking [59]. TQ was recently demonstrated to target microtubules, causing a time and dose-dependent degradation of α and β-tubulin in U87MG glioblastoma and Jurkat T lymphoblastic leukemia cells [54]. Taken together, these reports support our findings that TQ induces LMP and cathepsin translocation in glioblastoma cells.…”

Liraglutide protects Rin-m5f β cells by reducing procoagulant tissue factor activity and apoptosis prompted by microparticles under conditions mimicking Instant Blood-Mediated Inflammatory Reaction

“…After treatment, cells were washed twice with PBS and then lysed in TRIS buffer containing protease inhibitors (5 μg/mL leupeptin, 5 m m benzamidine) and 2% Triton ® X‐100 on ice. Total proteins (30 μg) were separated by electrophoresis on 10% SDS‐polyacrylamide (Sigma) gels as previously described . Blotting membranes were incubated with the primary mouse antibody for p‐IκBα (US Biological, Swampscott, MA, USA; 1:1000 dilution) or total IκBα (Millipore, Molsheim, France, 1:1000 dilution) overnight at 4 °C.…”

Antitumor Activity of Monoterpenes Found in Essential Oils

“…Das and collaborators [100] showed that thymoquinone and diosgenin, alone and in combination, inhibited cell proliferation and induced apoptosis in squamous cell carcinoma. Alhosin and collaborators [101] demonstrated that thymoquinone induced degradation of α - and β -tubulin proteins in human cancer cells without affecting their levels in normal human fibroblasts.…”