Molecular insight and preclinical perspective of thymoquinone as chemopreventive agent and therapeutic adjunct in cancer

Abstract

Thymoquinone (TQ) is the predominant bioactive constituent present in black seed oil (Nigella sativa) and tested for its anecdotal efficacy against several diseases including their potent anticancer and adjunctive therapeutic potential. We present information from literature highlighting molecular insight for anti-tumor functions of TQ largely due to its pleiotropic mechanism of action and ability to prevent tumor growth in preclinical models. Thymoquinone has anti-inflammatory effects and inhibits tumor cell proliferation through modulation of apoptosis signaling, inhibition of angiogenesis, metastasis and exert cytostatic as well as cytotoxic effect on several cancer cell lines. Collectively the results, thus far, points to efficacy of this compound in enhancing therapeutic benefit against tumors that are resistant to therapy. TQ targets cellular niches considered as molecular determinants for chemo resistant phenotype and responsible for their survival and progression. Novel analogs of TQ directed towards better efficacy and sensitizing potential than parent TQ have been reported. Further in-depth studies are warranted including investigation on its bioavailability and pharmacokinetics. From clinical perspective, information on maximum tolerated dose (MTD) and dosing schedule in human subjects are lacking in literature. Nevertheless, existing preclinical knowledge strongly support advancement of TQ to phase-I clinical trial for intervention strategies that prevent or slows down the disease process and contribute to reduced incidence of cancer.