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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 A5, 11 ; Hashemi M5, 12
Authors
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Authors Affiliations
  1. 1. School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
  3. 3. Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
  5. 5. Farhikhtegan Medical Convergent Sciences Research Center, TeMs. C., Islamic Azad University, Tehran, Iran
  6. 6. Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
  7. 7. Department of Biochemistry, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran
  8. 8. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  10. 10. Surgical Research Society (SRS), Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
  11. 11. Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  12. 12. Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

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.
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