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  1. Article ; Online: The Neem Limonoid Nimbolide Modulates Key Components of the DNA Damage Response Signalling in Cellular and Animal Models of Oral Squamous Cell Carcinoma

    Arvindh, Soundararajan / Priyadarshini, Manashi / Baba, Abdul Basit / Veeravarmal, Veeran / Mishra, Rajakishore / Dash, Rupesh / Nagini, Siddavaram

    Current pharmaceutical biotechnology

    2024  

    Language English
    Publishing date 2024-03-28
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2132197-8
    ISSN 1873-4316 ; 1389-2010
    ISSN (online) 1873-4316
    ISSN 1389-2010
    DOI 10.2174/0113892010291998240321074920
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6212: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Nimbolide, a Neem Limonoid, Inhibits Angiogenesis in Breast Cancer by Abrogating Aldose Reductase Mediated IGF-1/PI3K/Akt Signalling.

    Nivetha, Ramesh / Arvindh, Soundararajan / Baba, Abdul Basit / Gade, Deepak Reddy / Gopal, Gopisetty / K, Chitrathara / Reddy, Kallamadi Prathap / Reddy, G Bhanuprakash / Nagini, Siddavaram

    Anti-cancer agents in medicinal chemistry

    2022  Volume 22, Issue 14, Page(s) 2619–2636

    Abstract: Background & objective: The insulin/IGF-1R/PI3K/Akt signalling cascade is increasingly being linked to breast cancer development, with aldose reductase (AR) playing a key role in mediating the crosstalk between this pathway and angiogenesis. The current ...

    Abstract Background & objective: The insulin/IGF-1R/PI3K/Akt signalling cascade is increasingly being linked to breast cancer development, with aldose reductase (AR) playing a key role in mediating the crosstalk between this pathway and angiogenesis. The current study was designed to investigate whether nimbolide, a neem limonoid, targets the oncogenic signaling network to prevent angiogenesis in breast cancer.
    Methods: Breast cancer cells (MCF-7, MDA-MB-231), EAhy926 endothelial cells, MDA-MB-231 xenografted nude mice, and tumour tissues from breast cancer patients were used for the study. The expression of AR and key players in IGF-1/PI3K/Akt signaling and angiogenesis was evaluated by qRT-PCR, immunoblotting, and immunohistochemistry. Molecular docking and simulation, overexpression, and knockdown experiments were performed to determine whether nimbolide targets AR and IGF-1R.
    Results: Nimbolide inhibited AR with consequent blockade of the IGF-1/PI3K/Akt and /HIF-1alpha/VEGF signalling circuit by influencing the phosphorylation and intracellular localisation of key signaling molecules. The downregulation of DNMT-1, HDAC-6, miR-21, HOTAIR, and H19 with the upregulation of miR-148a/miR-152 indicated that nimbolide regulates AR and IGF-1/PI3K/Akt signaling via epigenetic modifications. Coadministration of nimbolide with metformin and the chemotherapeutic drugs tamoxifen/cisplatin displayed higher efficacy than single agents in inhibiting IGF-1/PI3K/Akt/AR signaling. Grade-wise increases in IGF-1R and AR expression in breast cancer tissues underscore their value as biomarkers of progression.
    Conclusion: This study provides evidence for the anticancer effects of nimbolide in cellular and mouse models of breast cancer besides providing leads for new drug combinations. It has also opened up avenues for investigating potential molecules such as AR for therapeutic targeting of cancer.
    MeSH term(s) Aldehyde Reductase ; Animals ; Azadirachta/chemistry ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Proliferation ; Endothelial Cells ; Female ; Humans ; Insulin-Like Growth Factor I/metabolism ; Insulin-Like Growth Factor I/pharmacology ; Limonins/pharmacology ; Mice ; Mice, Nude ; MicroRNAs/metabolism ; Molecular Docking Simulation ; Neovascularization, Pathologic/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction
    Chemical Substances Limonins ; MIRN152 microRNA, human ; MicroRNAs ; nimbolide (25990-37-8) ; Insulin-Like Growth Factor I (67763-96-6) ; Aldehyde Reductase (EC 1.1.1.21) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
    Language English
    Publishing date 2022-01-29
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2217610-X
    ISSN 1875-5992 ; 1871-5206
    ISSN (online) 1875-5992
    ISSN 1871-5206
    DOI 10.2174/1871520622666220204115151
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5583: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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