Review on molecular and therapeutic potential of thymoquinone in cancer

Abstract

Thymoquinone (TQ) is the predominant bioactive constituent present in black seed oil (Nigella sativa) and has been tested for its efficacy against cancer. Here, we summarize the literature about TQ's molecular mechanism of action and its ability to induce apoptosis and inhibit tumor growth in preclinical models. TQ has anti-inflammatory effects, and it inhibits tumor cell proliferation through modulation of apoptosis signaling, inhibition of angiogenesis, and cell cycle arrest. Chemosensitization by TQ is mostly limited to in vitro studies, and it has potential in therapeutic strategy for cancer. The results favor efficacy and enhancement of therapeutic benefit against tumor cells resistant to therapy based on cellular targets that are molecular determinants for cancer cell survival and progression. There have been attempts to synthesize novel analogs of TQ directed toward superior effects in killing tumor cells with more enhanced chemosensitizing potential than parent TQ compound. Based on published reports, we believe that further in-depth studies are warranted including investigation of its bioavailability and Phase I toxicity profiling in human subjects. The results from such studies will be instrumental in advancing this field in support of initiating clinical trials for testing the effects of this ancient agent in cancer therapy.

FIG. 1

Structure of thymoquinone (2-Isopropyl-5-methyl-1,4-benzoquinone).

FIG. 2

Multitargeted effects of thymoquinone. ROS, reactive oxygen species; DT, dehydragenase quinine; COX-2, cyclooxygenase-2, PGE-2; prostaglandin E-2; Bcl-2, B-cell non-Hodgkin lymphoma-2; Bax, Bcl-2-associated x protein; CHEK-1, checkpoint kinase 1 homolog; XIAP, x-linked inhibitor of apoptosis protein; E2F-1, E2F transcription factor 1; GATA, GATA transcription factor; UHRF, ubiquitin PHD RING finger; TNF α, tumor necrosis factor alpha; IL, interleukin; MCP-1, monocyte chemotactic protein-1; Muc-4, Mucin-4; VEGF, vascular endothelial growth factor; MAPK, mitogen-activated protein kinase.