Progress in the Development of Black Seed-Derived Anticancer Agents

Black seeds, in some form or the other, have remained popular in folklore medicine throughout the history of mankind. This herb has been used for millenniums to strengthen the immune system, cleanse the body, purify the blood, protect against irritants, and support health longevity. Not only do the scriptures from three major religions of the world (Judaism, Christianity, and Islam) endorse their health benefits, the use of black seed oil has been emphasized in the Mesopotamian, Greek, Indus Valley, Egyptian, and other important civilizations. Despite the unequivocal medicinal use of black seeds since ancient times, little was known in terms of its major active ingredients. Modern molecular research has expanded the repertoire of biological effects elicited by these intriguing seeds compelling the research community to characterize the main element responsible for the health benefits. The development of high-performance purification techniques allowed the parsing of the constituents of Black seeds to a much deeper level. These studies have concluded in the identification of Thymoquinone as the major component in black seeds that is responsible for the various biological effects, particularly its anticancer mechanism. These findings drove intense research in different laboratories all across the globe leading to considerable enhancement of our knowledge of Thymoquinone’s primary as well as interacting mechanisms against cancer cells. Despite the encouraging laboratory results in cancer cell lines and preclinical efficacy in animal tumor models, a major problem associated with Thymoquinone is its poor bioavailability. This serves as a major caveat and is therefore the chief hurdle blocking its translation as a therapeutic agent in the clinic. In order to overcome this problem, a number of novel analogues of Thymoquinone have been developed recently that have shown superior pharmacokinetic properties. These analogues show early promise at least in the preclinical setting and provide confidence for their future incorporation into clinical practice as single agent or part of a combination regimen for cancer treatment. Through this chapter, we bring forth a historical perspective on the different major milestones in Black seed anticancer research. The current knowledge on the progress of black seed-derived anticancer agents is highlighted along with a forward-looking view as to where the Thymoquinone-related research field might be heading.