A comprehensive view on the fisetin impact on colorectal cancer in animal models:Focusing on cellular and molecular mechanisms

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外文标题：A comprehensive view on the fisetin impact on colorectal cancer in animal models:Focusing on cellular and molecular mechanisms

外文摘要：Flavonoids,including fisetin,have been linked to a reduced risk of colorectal cancer(CRC)and have potential therapeutic applications for the condition.Fisetin,a natural flavonoid found in various fruits and vegetables,has shown promise in managing CRC due to its diverse biological activities.It has been found to influence key cell signaling pathways related to inflammation,angiogenesis,apoptosis,and transcription factors.The results of this study demonstrate that fisetin induces colon cancer cell apoptosis through multiple mechanisms.It impacts the p53 pathway,leading to increased levels of p53 and decreased levels of murine double minute 2,contributing to apoptosis induction.Fisetin also triggers the release of important components in the apoptotic process,such as second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pl and cytochrome c.Furthermore,fisetin inhibits the cyclooxygenase-2 and wingless-related integration site(Wnt)/epidermal growth factor receptor/nuclear factor kappa B signaling pathways,reducing Wnt target gene expression and hindering colony formation.It achieves this by regulating the activities of cyclin-dependent kinase 2 and cyclin-dependent kinase 4,reducing retinoblastoma protein phosphorylation,decreasing cyclin E levels,and increasing p21 levels,ulti-mately influencing E2 promoter binding factor 1 and cell division cycle 2(CDC2)protein levels.Additionally,fisetin exhibits various effects on CRC cells,including inhibiting the phosphorylation of Y-box binding protein 1 and ribosomal S6 kinase,promoting the phosphorylation of extracellular signal-regulated kinase 1/2,and disrupting the repair process of DNA double-strand breaks.Moreover,fisetin serves as an adjunct therapy for the prevention and treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α(PIK3CA)-mutant CRC,resulting in a reduction in phos-phatidylinositol-3 kinase(PI3K)expression,Ak strain transforming phosphorylation,mTOR activity,and downstream target proteins in CRC cells with a PIK3CA mutation.These findings highlight the multifaceted potential of fisetin in managing CRC and position it as a promising candidate for future therapy development.

外文关键词：

apoptosiscolorectal cancerfisetininflammationp53 pathway

作者：

Mohammad Yasin Zamanian、Niloofar Taheri、Montather F.Ramadan、Yasser Fakri Mustafa、Safa Alkhayyat、Klunko Nataliya Sergeevna、Hashem O.Alsaab、Ahmed Hjazi、Farnoosh Molavi Vasei、Siamak Daneshvar

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作者单位：

Department of Physiology,School of Medicine,Hamadan University of Medical Sciences,Hamadan,Iran

Department of Pharmacology and Toxicology,School of Pharmacy,Hamadan University of Medical Sciences,Hamadan,Iran

School of Medicine,Shahroud University of Medical Sciences,Shahroud,Iran

College of Dentistry,AI-Ayen University,Nasiriyah,Iraq

Department of Pharmaceutical Chemistry,College of Pharmacy,University of Mosul,Mosul,Iraq

College of Pharmacy,The Islamic University,Najaf,Iraq

Department of Training of Scientific and Scientific-Pedagogical Personnel,Russian New University,Moscow,Russian Federation

Department of Pharmaceutics and Pharmaceutical Technology,Taif University,Taif,Saudi Arabia

Department of Medical Laboratory,College of Applied Medical Sciences,Prince Sattam bin Abdulaziz University,Al-Kharj,Saudi Arabia

Department of Clinical Biochemistry,School of Medicine,Rafsanjan University of Medical Sciences,Rafsanjan,Iran

Department of Surgery,School of Medicine,Hamadan University of Medical Sciences,Hamadan,Iran

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关键词：

apoptosis colorectal cancer fisetin inflammation p53 pathway

出版年：

2024

DOI：

10.1002/ame2.12476

动物模型与实验医学(英文)

中国实验动物学会,中国医学科学院医学实验动物研究所

动物模型与实验医学(英文)

ISSN：2096-5451

年,卷(期)：2024.7(5)