Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies

Abstract

Background Cancer remains a critical global health challenge and a leading cause of mortality. Flavonoids found in fruits and vegetables have gained attention for their potential anti-cancer properties. Fisetin, abundantly present in strawberries, apples, onions, and other plant sources, has emerged as a promising candidate for cancer prevention. Epidemiological studies linking a diet rich in these foods to lower cancer risk have sparked extensive research on fisetin’s efficacy. Objective This review aims to comprehensively explore the molecular mechanisms of fisetin's anticancer properties and investigate its potential synergistic effects with other anticancer drugs. Furthermore, the review examines the therapeutic and preventive effects of fisetin against various cancers. Methods A systematic analysis of the available scientific literature was conducted, including research articles, clinical trials, and review papers related to fisetin’s anticancer properties. Reputable databases were searched, and selected studies were critically evaluated to extract essential information on fisetin’s mechanisms of action and its interactions with other anticancer drugs. Results Preclinical trials have demonstrated that fisetin inhibits cancer cell growth through mechanisms such as cell cycle alteration, induction of apoptosis, and activation of the autophagy signaling pathway. Additionally, fisetin reduces reactive oxygen species levels, contributing to its overall anticancer potential. Investigation of its synergistic effects with other anticancer drugs suggests potential for combination therapies. Conclusion Fisetin, a bioactive flavonoid abundant in fruits and vegetables, exhibits promising anticancer properties through multiple mechanisms of action. Preclinical trials provide a foundation for further exploration in human clinical trials. Understanding fisetin’s molecular mechanisms is vital for developing novel, safe, and effective cancer prevention and treatment strategies. The potential synergy with other anticancer drugs opens new avenues for combination therapies, enhancing cancer management approaches and global health outcomes.

Role of Fisetin in Selected Malignant Neoplasms in Women

“…The beneficial effects of fisetin against a wide variety of cancers have been unambiguously confirmed, as described by many authors in recent two decades [26,[35][36][37][38][39]. However, to the best of our knowledge, no dedicated review covering the research on anticancer activity of fisetin toward cancer cells derived from female malignancies has appeared as yet.…”

Exploring the Cellular Interactions of Flavonoids with Similar Structures in Cells Overexpressing the 70 kDa Human Heat Shock Protein

“…Fisetin acts antagonistically against Hsp70, inhibiting the heat shock-induced binding of HSF1 to the Hsp70 gene promoter, blocking transcription, and down-regulating protein expression. Therefore, fisetin acts as a potent inhibitor of HSF1, interfering with cancer cell proliferation, and causing apoptosis [33]. Fisetin also showed cytotoxic effects on normal NIH/3T3 cells by reducing their viability, in a study that investigated the anti-angiogenic and anti-cancer effects of this natural flavonoid [34].…”

Selected Flavonols Targeting Cell Death Pathways in Cancer Therapy: The Latest Achievements in Research on Apoptosis, Autophagy, Necroptosis, Pyroptosis, Ferroptosis, and Cuproptosis

“…Table 1. List of flavonols involved in the regulation of different types of cell death [7][8][9][10][11][12][13][14].…”