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Review
. 2012 Nov 15;84(10):1277-81.
doi: 10.1016/j.bcp.2012.07.012. Epub 2012 Jul 25.

Dietary flavonoid fisetin: a novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management

Vaqar Mustafa Adhami  1 , Deeba Nadeem Syed, Naghma Khan, Hasan Mukhtar
Affiliations
Review

Dietary flavonoid fisetin: a novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management

Vaqar Mustafa Adhami et al. Biochem Pharmacol. .

Abstract

Epidemiologic and case control population based studies over the past few decades have identified diet as an important determinant of cancer risk. This evidence has kindled interest into research on bioactive food components and has till date resulted in the identification of many compounds with cancer preventive and therapeutic potential. Among such compounds has been fisetin (3,7,3',4'-tetrahydroxyflavone), a flavonol and a member of the flavonoid polyphenols that also include quercetin, myricetin and kaempferol. Fisetin is commonly found in many fruits and vegetables such as apples, persimmons, grapes, kiwis, strawberries, onions and cucumbers. We evaluated the effects of fisetin against melanoma and cancers of the prostate, pancreas and the lungs. Using prostate and lung adenocarcinoma cells, we demonstrated that fisetin acts as a dual inhibitor of the PI3K/Akt and the mTOR pathways. This is a significant finding considering the fact that mTOR is phosphorylated and its activation is more frequent in tumors with overexpression of PI3K/Akt. Dual inhibitors of PI3K/Akt and mTOR signaling have been suggested as valuable agents for treating such cancers. Here, we summarize our findings on the dietary flavonoid fisetin and its effects on cancer with particular focus on prostate cancer. Our observations and findings from other laboratories suggest that fisetin could be a useful chemotherapeutic agent that could be used either alone or as an adjuvant with conventional chemotherapeutic drugs for the management of prostate and other cancers.

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Figures

Figure 1
Figure 1. Graphic representation of the effect of fisetin on PI3K/Akt/mTOR signaling
Simultaneously targeting both PI3K/Akt and mTOR has the potential to inhibit both upstream and downstream signaling in the pathway. Fisetin inhibits the mTOR pathway and keeps the feedback loop in check by also inhibiting the PI3K/Akt pathway and inhibits cell survival and growth.
See this image and copyright information in PMC

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