ArticleScientific reports2016
Nimbolide, a neem limonoid inhibits Phosphatidyl Inositol-3 Kinase to activate Glycogen Synthase Kinase-3β in a hamster model of oral oncogenesis.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 44 citations in OpenAlex.
- The Neem Limonoid Nimbolide Modulates Key Components of the DNA Damage Response Signalling in Cellular and Animal Models of Oral Squamous Cell Carcinoma.Current pharmaceutical biotechnology · 2025Article
- Zeolitic Imidazole Framework/Silica Nanocomposite for Targeted Cancer Therapeutics: Comparative Study of Chemo-Drug Cisplatin (CPt) and Green Platinum (GPt) Efficacy.International journal of molecular sciences · 2024Article
- Nimbolide: promising agent for prevention and treatment of chronic diseases (recent update).Food & nutrition research · 2024Article
- Tolypothrix Dichloromethane Ethylacetate fraction (TDEF) inhibits cisplatin resistance H357 cell through PI3K/AKT/beta-catenin pathway.American journal of cancer research · 2024Article
- Targeting the DENV NS2B-NS3 protease with active antiviral phytocompounds: structure-based virtual screening, molecular docking and molecular dynamics simulation studies.Journal of molecular modeling · 2022Article
- Exploring the therapeutic potential of Neem (Annals of translational medicine · 2022Review
- Comprehending the crosstalk between Notch, Wnt and Hedgehog signaling pathways in oral squamous cell carcinoma - clinical implications.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Nimbolide inhibits tumor growth by restoring hepatic tight junction protein expression and reduced inflammation in an experimental hepatocarcinogenesis.World journal of gastroenterology · 2020Article
- Wnt/β-Catenin Signaling in Oral Carcinogenesis.International journal of molecular sciences · 2020Review
- Review
- Nimbolide, a neem limonoid inhibits cytoprotective autophagy to activate apoptosis via modulation of the PI3K/Akt/GSK-3β signalling pathway in oral cancer.Cell death & disease · 2018Article
- Tracing the biosynthetic origin of limonoids and their functional groups through stable isotope labeling and inhibition in neem tree (Azadirachta indica) cell suspension.BMC plant biology · 2018Article
- Limonoids from seeds ofActa pharmaceutica Sinica. B · 2018Article
- Nimbolide upregulates RECK by targeting miR-21 and HIF-1α in cell lines and in a hamster oral carcinogenesis model.Scientific reports · 2017Article
- Inhibition of cell survival and proliferation by nimbolide in human androgen-independent prostate cancer (PC-3) cells: involvement of the PI3K/Akt pathway.Molecular and cellular biochemistry · 2017Article
- A review of the anticancer activity of Azadirachta indica (Neem) in oral cancer.Journal of oral biology and craniofacial researchArticle
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycogen synthase kinase-3β (GSK-3β), a serine/threonine kinase is frequently inactivated by the oncogenic signalling kinases PI3K/Akt and MAPK/ERK in diverse malignancies. The present study was designed to investigate GSK-3β signalling circuits in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model and the therapeutic potential of the neem limonoid nimbolide. Inactivation of GSK-3β by phosphorylation at serine 9 and activation of PI3K/Akt, MAPK/ERK and β-catenin was associated with increased cell proliferation and apoptosis evasion during stepwise evolution of HBP carcinomas. Administration of nimbolide inhibited PI3K/Akt signalling with consequent activation of GSK-3β thereby inducing trafficking of β-catenin away from the nucleus and enhancing the expression of miR-126 and let-7. Molecular docking studies confirmed interaction of nimbolide with PI3K, Akt, ERK and GSK-3β. Furthermore, nimbolide attenuated cell proliferation and induced apoptosis as evidenced by increased p-cyclin D1(Thr286) and pro-apoptotic proteins. The present study has unravelled aberrant phosphorylation as a key determinant for oncogenic signalling and acquisition of cancer hallmarks in the HBP model. The study has also provided mechanistic insights into the chemotherapeutic potential of nimbolide that may be a useful addition to the armamentarium of natural compounds targeting PI3K for oral cancer treatment.
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