Repurposing Natural Dietary Flavonoids in the Modulation of Cancer Tumorigenesis: Decrypting the Molecular Targets of Naringenin, Hesperetin and Myricetin

In the past few years flavonoids have been gaining more attention regarding their (still un) exploited anticancer properties. Flavonoids are natural compounds present in fruits, vegetables, and seeds, meaning that they are already present in the daily life of every person, with a described broad-spectrum of pharmacological activities, including anticancer, anti-inflammatory and antioxidant. In the present review we discuss the anticancer activity of three important flavonoids - myricetin (MYR) (flavanol group), hesperetin (HESP) and naringenin (NAR) (flavanone group). Although some mechanisms underlying their activities remain still unclear, they can act as potential inhibitors of key tumorigenic signaling pathways, such as PI3K/Akt/mTOR, p38 MAPK and NF-κB. Simultaneously, they can reset the levels of pro-apoptotic proteins that belong to the Bcl-2 and caspase family and decrease the intracellular levels of ROS and pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6. Together with their synergetic effect they have the potential to become key elements in the prevention and/or treatment of several types of cancer, with the major improvement to the patient life quality, due to their non-existent toxicity.