Dietary flavonoid fisetin for cancer prevention and treatment

Abstract

Cancer remains a major public health concern and a significant cause of death worldwide. Identification of bioactive molecules that have the potential to inhibit carcinogenesis continues to garner interest among the scientific community. In particular, flavonoids from dietary sources are the most sought after because of their safety, cost-effectiveness, and feasibility of oral administration. Emerging data have provided newer insights into understanding the molecular mechanisms that are essential to identify novel mechanism-based strategies for cancer prevention and treatment. Dietary flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) found in many fruits and vegetables has been shown in preclinical studies to inhibit cancer growth through alteration of cell cycle, inducing apoptosis, angiogenesis, invasion, and metastasis without causing any toxicity to normal cells. Although data from in-vitro and in-vivo studies look convincing, well-designed clinical trials in humans are needed to conclusively determine the efficacy across various cancers. This review highlights the chemopreventive and therapeutic effects, molecular targets, and mechanisms that contribute to the observed anticancer activity of fisetin against various cancers.

Keywords: Cancer; Chemoprevention; Diet; Fisetin; Flavonoid.

Figure 1.

Structure and basic properties of fisetin. (A) The chemical structure of fisetin (3, 7, 3′, 4′-tetrahydroxyflavone). (B) Major physical and chemical properties of fisetin.

Figure 2.

Molecular targets of fisetin in various cancers. Fisetin interacts with multiple cellular targets by binding to and interacting with several molecular targets fisetin regulates a wide variety of cell functions. Fisetin disrupts Wnt signaling and results in cell cycle arrest. It inhibits the YB-1 binding protein to suppress epithelial to mesenchymal transition and thus prevents invasion and migration of cancer cells. By physically interacting with the mTOR molecule, fisetin inhibits signaling involved in cell survival thus explaining its inhibitory effect on cellular growth and proliferation. Fisetin binds to and disrupts microtubule dynamics and acts as a stabilizing agent with effects far superior to paclitaxel. However across all cancers, mTOR and NF-kB appear to be the most commonly affected pathways.