Fisetin as a chemoprotective and chemotherapeutic agent: mechanistic insights and future directions in cancer therapy

Cancer remains a leading cause of mortality globally, characterized by the uncontrolled proliferation of abnormal cells, invasion of healthy tissues, and potential metastasis. Natural compounds have become a focus in cancer research due to their potential therapeutic roles. Among these, fisetin, a dietary flavonoid, demonstrates notable anti-cancer properties through various molecular mechanisms. This review evaluates the chemoprotective and chemotherapeutic potential of fisetin, focusing on its mechanisms of action against cancer and its capacity to enhance cancer treatment. A systematic literature search was conducted across PubMed, Web of Science, and Scopus databases using keywords related to fisetin and cancer. The review synthesizes findings from in vitro and in vivo studies examining fisetin’s effects on signaling pathways, apoptosis induction, oxidative stress modulation, and synergistic potential with chemotherapeutic agents. Fisetin has shown the ability to suppress tumor growth and metastasis by modulating critical signaling pathways, including PI3K/Akt/mTOR, NF-κB, and MAPK. It induces apoptosis in cancer cells through mitochondrial and endoplasmic reticulum stress responses and demonstrates antioxidative properties by reducing reactive oxygen species. Additionally, fisetin enhances the efficacy of conventional chemotherapies, indicating its role as a potential adjuvant in cancer treatment. Fisetin presents a promising natural compound with diverse anti-cancer effects, impacting cell cycle arrest, apoptosis, and oxidative stress pathways. Further clinical studies are warranted to fully elucidate its therapeutic potential and to optimize its delivery for improved bioavailability in cancer patients.