Anti-cancer properties and mechanisms of action of thymoquinone, the major active ingredient ofNigella sativa

Abstract

Over the past two decades, studies have documented the wide-range anti-cancer effects of Nigella sativa, known as black seed or black cumin. Thymoquinone (TQ), its major active ingredient, has also been extensively studied and reported to possess potent anti-cancer properties. Herein, we provide a comprehensive review of the findings related to the anti-cancer activity of TQ. The review focuses on analyzing experimental studies performed using different in vitro and in vivo models to identify the anti-proliferative, pro-apoptotic, anti-oxidant, cytotoxic, anti-metastatic, and NK-dependent cytotoxic effects exerted by TQ. In addition, we pinpoint the molecular mechanisms underlying these effects and the signal transduction pathways implicated by TQ. Our analysis show that p53, NF-κB, PPARγ, STAT3, MAPK, and PI3K/AKT signaling pathways are among the most significant pathways through which TQ mediates its anti-cancer activity. Experimental findings and recent advances in the field highlight TQ as an effective therapeutic agent for the suppression of tumor development, growth and metastasis for a wide range of tumors.

Thymoquinone Can Improve Neuronal Survival and Promote Neurogenesis in Rat Hippocampal Neurons

“…[54] Especially in cancer cells, TQ also showed a hindering effect on proliferation due to over-phosphorylation of some protein kinases such as AKT, ERK, and JNK. [55,56] Herein, we observed that an increase in the phosphorylation of all studied kinases (GSK-3, ERK1/2, and JNK-2) and factors (CREB) except activation of AKT suggesting the activation of a cell survival cascade parallel to the increase in the surviving neurons in hippocampal regions by TQ administration. GSK-3 may be a sensor determining the neuronal cell fate in the brain and GSK-3β, which is active in resting cells, is inactivated by phosphorylation.…”

Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies

“…Reportedly, TQ interferes in the phosphorylation and subsequent activation of several upstream tyrosine kinases (e.g., MAPK, Akt, mTOR, PIP3) that are involved in tumor cell proliferation signaling pathways (Yi et al, 2008; Kundu et al, 2014b). Transcriptional factors (e.g., Nrf2, NF-κB, and STAT-3), key players in various oncogenesis process, are other crucial molecular targets of TQ (Kundu et al, 2014b; Darakhshan et al, 2015; Majdalawieh et al, 2017). By regulating the activation of these transcription factors, TQ can counteract different tumorigenic processes including inflammation, cell proliferation, cell survival, angiogenesis, cell invasions, and metastasis.…”

“…of TQ have been identified that are somehow involved in tumorigenesis or development of drug resistance (Kundu et al, 2014b) (Figure 1). Though treatment with TQ alone has shown antitumor efficacy in several in vitro and in vivo studies as mentioned in details in a recent review (Majdalawieh et al, 2017), the lower efficacy (Effenberger et al, 2010) and poor bioavailability (Ganea et al, 2010; Elmowafy et al, 2016) of TQ is the primary bottleneck for considering it as the primary therapeutic agent. Therefore, in this review, we proposed the potential role of TQ as an adjuvant therapy with different types of conventional cancer treatments namely surgery, radiotherapy, chemotherapy, and immunotherapy either to prevent carcinogenesis or to potentiate the efficiency of conventional therapeutic modalities.…”

Protective role of Nigella sativa in chemotherapy-induced alopecia

“…Moreover, N. sativa also contains It is evident from the previous multiple studies that N. sativa showed cytotoxic effects in different types of cancer including lung cancer, breast cancer, cervical cancer, ovarian cancer and colorectal cancer (Majdalawieh and Fayyad, 2016). N. sativa showed cytotoxic, anti -proliferative, pro-apoptotic, anti-oxidant, anti-metastatic, and NK-dependent cytotoxic effects due to its main constituent thymoquinone (Majdalawieh et al, 2017). As N. sativa have promising results for the treatment of cancer.…”