Modulation of the Pi3k/Akt Signaling Pathway by Resveratrol in Cancer: Molecular Mechanisms and Therapeutic Opportunity Publisher



Hedayati N¹ ; Safari MH² ; Milasi YE³ ; Kahkesh S⁴ ; Farahani N⁵ ; Khoshnazar SM⁶ ; Dorostgou Z⁷ ; Alaei E⁸ ; Alimohammadi M⁹ ; Rahimzadeh P¹⁰ ; Taheriazam A^{5, 11} ; Hashemi M^{5, 12}
Source: Discover Oncology Published:2025

Abstract

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is a critical intracellular signaling pathway that is pivotal in various cellular functions. It is in senescence, survival, and growth under normal physiological and pathological conditions, including neoplasms. Additionally, this pathway has been recognized as essential for the regulation of the cell cycle. Several previous studies have indicated that the PI3K/Akt signaling pathway can be influenced by various natural products, with resveratrol (3,4′,5-trihydroxy-trans-stilbene) being a particularly important phytoalexin polyphenol in this context. This review explores the impact of the PI3K/Akt signaling pathway on the initiation and advancement of various cancerous conditions and the potential of resveratrol to target this signaling mechanism. The review begins by summarizing the anti-tumor capabilities of resveratrol and then emphasizes the significant role of the PI3K/Akt signaling pathway in the progression of multiple malignancies. Finally, we discuss the therapeutic effects of resveratrol on human neoplasms, from brain cancers to gastrointestinal malignancies, through regulation of this signaling cascade. © The Author(s) 2025.