Cancer chemopreventive role of fisetin: Regulation of cell signaling pathways in different cancers. (October 2021)

• Record Type: Journal Article
• Authors: Farooqi, Ammad Ahmad; Naureen, Humaira; Zahid, Rabbia; Youssef, Lara; Attar, Rukset; Xu, Baojun
• Is Part Of: Pharmacological research. Volume 172(2021)
• Publication Date: 2021-10
• Subjects: PRAS40 Proline-rich Akt substrate -- S6K ribosomal S6 kinase -- 4EBP eIF4Ebinding protein 1 -- TSC2 Tuberous sclerosis complex-2 -- RAPTOR Regulatory Associated Protein of mTOR -- RICTOR Rapamycin-Insensitive Companion of mTOR -- LRP5/6 Low-density lipoprotein receptor-related proteins 5/6 -- DKK1 Dickkopf Wnt Signaling pathway inhibitor -- SFRPs secreted Frizzled-related proteins -- WIF Wnt inhibitory factor -- FasL Fas ligand -- TRAIL Tumor necrosis factor-related apoptosis-inducing ligand -- XIAP X-Linked Inhibitor of Apoptosis -- SMAC Second Mitochondria-derived Activator of Caspase -- DIABLO Direct IAP-Binding protein with Low pI -- IRE1 Inositol-requiring enzyme-1 -- ATF4 activating transcription factor-4 -- PERK protein kinase RNA-like ER kinase -- VEGF Vascular Endothelial Growth Factor -- IKK inhibitor of IκB kinase -- TET Ten-eleven translocation -- ZAK Leucine zipper-and sterile alpha Motif-containing Kinase -- LATS1/ LATS2 large tumor suppressors; Fisetin (PubChem CID: 5281614) -- Sorafenib (PubChem CID: 9826472) -- Carnosic acid (PubChem CID: 65126) -- Cabazitaxel (PubChem CID: 9854073) -- Necrostatin (PubChem CID: 2828334); Fisetin -- Cancer prevention -- Cell signaling pathway -- PI3K/AKT/mTOR -- Wnt/β-catenin -- TRAIL/TRAIL-R; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105784
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: It is becoming progressively more understandable that pharmaceutical targeting of drug-resistant cancers is challenging because of intra- and inter-tumor heterogeneity. Interestingly, naturally derived bioactive compounds have unique ability to modulate wide-ranging deregulated oncogenic cell signaling pathways. In this review, we have focused on the available evidence related to regulation of PI3K/AKT/mTOR, Wnt/ β -catenin, NF-κB and TRAIL/TRAIL-R by fisetin in different cancers. Fisetin has also been shown to inhibit the metastatic spread of cancer cells in tumor-bearing mice. We have also summarized how fisetin regulated autophagy in different cancers. In addition, this review also covers fisetin-mediated regulation of VEGF/VEGFR, EGFR, necroptosis and Hippo pathway. Fisetin has entered into clinical trials particularly in context of COVID19-associated inflammations. Furthermore, fisetin mediated effects are also being tested in clinical trials with reference to osteoarthritis and senescence. These developments will surely pave the way for full-fledge and well-designed clinical trials of fisetin in different cancers. However, we still have to comprehensively analyze and fully unlock pharmacological potential of fisetin against different oncogenic signaling cascades and non-coding RNAs. Fisetin has remarkable potential as chemopreventive agent and future studies must converge on the identification of additional regulatory roles of fisetin for inhibition and prevention of cancers. Graphical Abstract: ga1