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. 2022 Jun 23;14(13):2604.
doi: 10.3390/nu14132604.

Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review

Robert Kubina  1   2 , Kamil Krzykawski  2 , Agata Kabała-Dzik  1 , Robert D Wojtyczka  3 , Ewa Chodurek  4 , Arkadiusz Dziedzic  5
Affiliations

Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review

Robert Kubina et al. Nutrients. .

Abstract

Diet plays a crucial role in homeostasis maintenance. Plants and spices containing flavonoids have been widely used in traditional medicine for thousands of years. Flavonols present in our diet may prevent cancer initiation, promotion and progression by modulating important enzymes and receptors in signal transduction pathways related to proliferation, differentiation, apoptosis, inflammation, angiogenesis, metastasis and reversal of multidrug resistance. The anticancer activity of fisetin has been widely documented in numerous in vitro and in vivo studies. This review summarizes the worldwide, evidence-based research on the activity of fisetin toward various types of cancerous conditions, while describing the chemopreventive and therapeutic effects, molecular targets and mechanisms that contribute to the observed anticancer activity of fisetin. In addition, this review synthesized the results from preclinical studies on the use of fisetin as an anticancer agent. Based on the available literature, it might be suggested that fisetin has a bioactive potential to become a complementary drug in the prevention and treatment of cancerous conditions. However, more in-depth research is required to validate current data, so that this compound or its derivatives can enter the clinical trial phase.

Keywords: anticancer; cancer; fisetin; flavonoid; flavonol.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The chemical structure and formula of flavonoids, flavonols and fisetin.
Figure 2
Figure 2
The potential mechanisms of cell-cycle inhibition of liver cancer cells (hepatocellular cancer, HCC) by modulation of several regulatory proteins under the influence of fisetin such as CDK4, Cyclin-dependent kinase 4; CDK6, Cyclin-dependent kinase 6; Cyclin D; CDK2, Cyclin-dependent kinase 2; CIP/KIP, the Cip/Kip family, namely, p21(Cip1), p27(Kip1) and p57(Kip2); CDK1, Cyclin-dependent kinase 1; CDC25C, M-phase inducer phosphatase 3; CDK3, Cyclin-dependent kinase 3; CHK1, Checkpoint kinase 1; CHK2, Checkpoint kinase 2; ATM, serine/threonine kinase; ATR, Serine/threonine-protein kinase; AuroraB, Aurora kinase B; AuroraA, Aurora kinase A; E2F, E2 transcription factors.
Figure 3
Figure 3
The multilevel, ultracellular effects of fisetin on major signalings that are involved in various cancers.
See this image and copyright information in PMC

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