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Flavonoids and PI3K/Akt/mTOR signaling cascade: A potential crosstalk in anticancer treatment

Journal

CURRENT MEDICINAL CHEMISTRY
Volume 28, Issue 39, Pages 8083-8097

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867328666210804091548

Keywords

Anthocyanins; cancer prevention; fisetin; flavonols; flavanones; hesperidin; isorhamnetin; kaempferol; mTOR; naringin; quercetin

Funding

  1. Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia [IFPRP: 118-141-1442]

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This paper discusses the current treatment options for cancer and the potential advantages of plant-based medicines, particularly the role of flavonoids in anticancer activities. Research targeting the PI3K/Akt/mTOR signaling pathway is crucial for the development of anticancer compounds.
Cancer is one of the leading causes of death worldwide. A slight decline in mortality has been noted, but the currently available treatment options did not give an expected outcome and are associated with several side effects resulting a substantial economic burden. The advent of plant-based treatment is rising because of its ease of use, ready availability, cost-effectiveness, and low/no toxicity. In recent years, flavonoids with their diverse physico-biological properties have gained the scientific community's attention for the treatment of various forms of cancer. Different flavonoids, especially, flavonols (quercetin, kaempferol, fisetin, and isorhamnetin), flavanones (hesperidin and naringin), and anthocyanins, have shown potent anticancer activities affecting various signaling cascades. Among those, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling pathway is widely known to play a significant role in different physio-cellular activities, which triggers malignant transformation and is considered a key target for anticancer compounds. This pathway plays a vital role in regulating the cell cycle, metabolism, survival, and proliferation. The flavonoids exhibit their anticancer activity via different molecular pathways, including PI3K/Akt/mTOR. In the current piece of paper, our focus is to underpin the action of the above-mentioned flavonoids against different cancers, mainly covering in-vitro data, through PI3K/Akt/mTOR targeting.

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