Inhibition of Akt/mTOR Signaling by the Dietary Flavonoid Fisetin
Deeba N. Syed,
Vaqar M. Adhami,
Mohammad Imran Khan,
Plants have long been providing mankind with remedies of different ailments. Flavonoids, a family of naturally occurring
polyphenolic compounds are ubiquitous in plants. Development of polyphenol-based drugs has not attracted much attention by
researchers and drug companies. Therefore, despite extensive studies on polyphenols, this vast group of compounds is underrepresented
in clinical medicine. Fisetin (3,7,3',4'-tetrahydroxyflavone) belongs to the flavonol subgroup of flavonoids together with quercetin,
myricetin and kaempferol and is found in several fruits and vegetables including strawberries, apples, persimmons and onions. Fisetin is
showing promise as a useful natural agent against cancer and has been evaluated for its potential inhibitory role against cancer in several
in vitro and in vivo studies. The Akt/mTOR pathway is known to play a central role in various cellular processes that contribute to the
malignant phenotype. Accordingly, inhibition of this signaling cascade has been a focus of recent therapeutic studies. Novel inhibitors of
PI3-K, Akt, and mTOR are now passing through early phase clinical trials. Herein, we review the effect of fisetin on the PI3-
K/Akt/mTOR pathway as studied in different cancer cell models.
Keywords: Fisetin, Akt, mTOR, lung cancer, prostate cancer, colon cancer, myeloma, melanoma.
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