Modulation of the PI3K/Akt signaling pathway by resveratrol in cancer: molecular mechanisms and therapeutic opportunity

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...

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Main Authors: Neda Hedayati, Mohamad Hosein Safari, Yaser Eshaghi Milasi, Samaneh Kahkesh, Najma Farahani, Seyedeh Mahdieh Khoshnazar, Zahra Dorostgou, Elmira Alaei, Mina Alimohammadi, Payman Rahimzadeh, Afshin Taheriazam, Mehrdad Hashemi
Format: Article
Language:English
Published: Springer 2025-05-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02471-w
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author Neda Hedayati
Mohamad Hosein Safari
Yaser Eshaghi Milasi
Samaneh Kahkesh
Najma Farahani
Seyedeh Mahdieh Khoshnazar
Zahra Dorostgou
Elmira Alaei
Mina Alimohammadi
Payman Rahimzadeh
Afshin Taheriazam
Mehrdad Hashemi
author_facet Neda Hedayati
Mohamad Hosein Safari
Yaser Eshaghi Milasi
Samaneh Kahkesh
Najma Farahani
Seyedeh Mahdieh Khoshnazar
Zahra Dorostgou
Elmira Alaei
Mina Alimohammadi
Payman Rahimzadeh
Afshin Taheriazam
Mehrdad Hashemi
author_sort Neda Hedayati
collection DOAJ
description 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.
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spelling doaj-art-d273b7ce73a940edac12baa7c2a7ff832025-08-20T03:09:20ZengSpringerDiscover Oncology2730-60112025-05-0116112410.1007/s12672-025-02471-wModulation of the PI3K/Akt signaling pathway by resveratrol in cancer: molecular mechanisms and therapeutic opportunityNeda Hedayati0Mohamad Hosein Safari1Yaser Eshaghi Milasi2Samaneh Kahkesh3Najma Farahani4Seyedeh Mahdieh Khoshnazar5Zahra Dorostgou6Elmira Alaei7Mina Alimohammadi8Payman Rahimzadeh9Afshin Taheriazam10Mehrdad Hashemi11School of Medicine, Iran University of Medical SciencesDepartment of Internal Medicine, Faculty of Veterinary Medicine, University of TehranDepartment of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical SciencesFaculty of Science, Shahid Chamran University of AhvazFarhikhtegan Medical Convergent Sciences Research Center, TeMs. C., Islamic Azad UniversityGastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical SciencesDepartment of Biochemistry, Neyshabur Branch, Islamic Azad UniversitySchool of Medicine, Tehran University of Medical SciencesDepartment of Immunology, School of Medicine, Shahid Beheshti University of Medical SciencesSurgical Research Society (SRS), Students’ Scientific Research Center, Tehran University of Medical SciencesFarhikhtegan Medical Convergent Sciences Research Center, TeMs. C., Islamic Azad UniversityFarhikhtegan Medical Convergent Sciences Research Center, TeMs. C., Islamic Azad UniversityAbstract 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.https://doi.org/10.1007/s12672-025-02471-wNeoplasmsPhosphatidylinositol 3-kinase signal transductionProto-oncogene protein AktResveratrol
spellingShingle Neda Hedayati
Mohamad Hosein Safari
Yaser Eshaghi Milasi
Samaneh Kahkesh
Najma Farahani
Seyedeh Mahdieh Khoshnazar
Zahra Dorostgou
Elmira Alaei
Mina Alimohammadi
Payman Rahimzadeh
Afshin Taheriazam
Mehrdad Hashemi
Modulation of the PI3K/Akt signaling pathway by resveratrol in cancer: molecular mechanisms and therapeutic opportunity
Discover Oncology
Neoplasms
Phosphatidylinositol 3-kinase signal transduction
Proto-oncogene protein Akt
Resveratrol
title Modulation of the PI3K/Akt signaling pathway by resveratrol in cancer: molecular mechanisms and therapeutic opportunity
title_full Modulation of the PI3K/Akt signaling pathway by resveratrol in cancer: molecular mechanisms and therapeutic opportunity
title_fullStr Modulation of the PI3K/Akt signaling pathway by resveratrol in cancer: molecular mechanisms and therapeutic opportunity
title_full_unstemmed Modulation of the PI3K/Akt signaling pathway by resveratrol in cancer: molecular mechanisms and therapeutic opportunity
title_short Modulation of the PI3K/Akt signaling pathway by resveratrol in cancer: molecular mechanisms and therapeutic opportunity
title_sort modulation of the pi3k akt signaling pathway by resveratrol in cancer molecular mechanisms and therapeutic opportunity
topic Neoplasms
Phosphatidylinositol 3-kinase signal transduction
Proto-oncogene protein Akt
Resveratrol
url https://doi.org/10.1007/s12672-025-02471-w
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