KRAS Mutation Reduces Thymoquinone Anticancer Effects on Viability of Cells and Apoptosis

Background: Cancer is a life-threatening condition with an economic burden on societies. Phytotherapy is rapidly taking place in cancer research to increase the success of treatment and quality of life. Thymoquinone (TQ) is the main active phenolic compound obtained from the essential oil of the Nigella sativa (black cumin) plant seed. For a long time, black cumin has been used traditionally for the remedy of different diseases because of its various biological effects. It has been shown that most of these effects of black cumin seeds are due to TQ. TQ became a popular research topic for phytotherapy studies for its potential therapeutic applications, and more research is going on to fully understand its mechanisms of action, safety, and efficacy in humans. KRAS is a gene that regulates cell division and growth. Monoallelic variants in KRAS result in uncontrollable cell division, leading to cancer development. Studies have shown that cancer cells with KRAS mutations are often resistant to certain types of chemotherapy and targeted therapies. Objective: This study aimed to compare the effect of TQ on cancer cells with and without KRAS mutation to better understand the reason why TQ may have different anticancer effects in the different types of cancer cells. Methods: TQ was investigated for its cytotoxic and apoptotic effects in laryngeal cancer cells (HEp-2) without KRAS mutation and compared to mutant KRAS-transfected larynx cancer cells and KRAS mutation-carrying lung cancer cells (A549). Results: We showed that TQ has more cytotoxic and apoptotic effects on laryngeal cancer cells without KRAS mutation than in cells with mutation. Conclusion: KRAS mutations decrease the effect of TQ on cell viability and apoptosis, and further studies are needed to fully understand the relationship between KRAS mutations and thymoquinone effectiveness in cancer treatment.