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  1. Article ; Online: Steroidal alkaloid solanidine impedes hypoxia-driven ATM phosphorylation to switch on anti-angiogenesis in lung adenocarcinoma.

    Sherapura, Ankith / Siddesh, B M / Malojirao, Vikas H / Thirusangu, Prabhu / Avin, B R Vijay / Kumari, N Suchetha / Ramachandra, Y L / Prabhakar, B T

    Phytomedicine : international journal of phytotherapy and phytopharmacology

    2023  Volume 119, Page(s) 154981

    Abstract: Purpose: The declined oxygen tension in the cancer cell leads to the hypoxic adaptive response and favors establishment of tumor micro environment [TEM]. The complex TME consists of interwoven hypoxic HIF-1α and DNA damage repair ATM signaling. The ATM/ ... ...

    Abstract Purpose: The declined oxygen tension in the cancer cell leads to the hypoxic adaptive response and favors establishment of tumor micro environment [TEM]. The complex TME consists of interwoven hypoxic HIF-1α and DNA damage repair ATM signaling. The ATM/HIF-1α phosphorylation switch on angiogenesis and abort apoptosis. Targeting this signaling nexus would be a novel therapeutic strategy for the treatment of cancer.
    Background: Steroidal alkaloid solanidine is known for varied pharmacological role but with less molecular evidences. Our earlier findings on solanidine proven its anti-neoplastic activity by inducing apoptosis in lung cancer. In continued research, efforts have been made to establish the underlying molecular signaling in induction of DNA damage in prevailing hypoxic TME.
    Methods: The solanidine induced DNA damage was assessed trough alkali COMET assay; signaling nexus and gene expression profile analysis through IB, qRT-PCR, Gelatin Zymography, IHC, IF and ELISA. Pathophysiological modulations assessed through tube formation, migration, invasion assays. Anti-angiogenic studies through CAM, rat aorta, matrigel assays and corneal neovascularization assay. Anti-tumor activity through in-vivo DLA ascites tumor model and LLC model.
    Results: The results postulates, inhibition of hypoxia driven DDR proteins pATM
    MeSH term(s) Rats ; Animals ; Phosphorylation ; Antineoplastic Agents/therapeutic use ; Hypoxia/drug therapy ; Alkaloids/pharmacology ; Adenocarcinoma of Lung/drug therapy ; Lung Neoplasms/drug therapy ; Hypoxia-Inducible Factor 1, alpha Subunit ; Neovascularization, Pathologic/drug therapy ; Cell Line, Tumor ; Tumor Microenvironment
    Chemical Substances solanidine (W7801OHM8B) ; Antineoplastic Agents ; Alkaloids ; Hypoxia-Inducible Factor 1, alpha Subunit
    Language English
    Publishing date 2023-07-18
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1205240-1
    ISSN 1618-095X ; 0944-7113
    ISSN (online) 1618-095X
    ISSN 0944-7113
    DOI 10.1016/j.phymed.2023.154981
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Steroidal alkaloid solanidine impedes hypoxia-driven ATM phosphorylation to switch on anti-angiogenesis in lung adenocarcinoma

    Sherapura, Ankith / Siddesh, B.M. / Malojirao, Vikas H. / Thirusangu, Prabhu / Avin, B.R. Vijay / Kumari, N Suchetha / Ramachandra, Y.L. / Prabhakar, B.T.

    Phytomedicine. 2023 July 18, p.154981-

    2023  , Page(s) 154981–

    Abstract: The declined oxygen tension in the cancer cell leads to the hypoxic adaptive response and favors establishment of tumor micro environment [TEM]. The complex TME consists of interwoven hypoxic HIF-1α and DNA damage repair ATM signaling. The ATM/HIF-1α ... ...

    Abstract The declined oxygen tension in the cancer cell leads to the hypoxic adaptive response and favors establishment of tumor micro environment [TEM]. The complex TME consists of interwoven hypoxic HIF-1α and DNA damage repair ATM signaling. The ATM/HIF-1α phosphorylation switch on angiogenesis and abort apoptosis. Targeting this signaling nexus would be a novel therapeutic strategy for the treatment of cancer. Steroidal alkaloid solanidine is known for varied pharmacological role but with less molecular evidences. Our earlier findings on solanidine proven its anti-neoplastic activity by inducing apoptosis in lung cancer. In continued research, efforts have been made to establish the underlying molecular signaling in induction of DNA damage in prevailing hypoxic TME. The solanidine induced DNA damage was assessed trough alkali COMET assay; signaling nexus and gene expression profile analysis through by IB, qRT-PCR, Gelatin Zymography, IHC, IF and ELISA. Pathophysiological modulations assessed through tube formation, migration, invasion assays. Anti-angiogenic studies through CAM, rat aorta, matrigel assays and corneal neo-vascularization assay. Anti-tumor activity through in-vivo DLA ascites tumor model and LLC model. The results postulates, inhibition of hypoxia driven DDR proteins pATMˢᵉʳ¹⁹⁸¹/pHIF-1αˢᵉʳ⁶⁹⁶ by solanidine induces anti-angiogenesis. Systematic study of both non-tumorigenic and tumorigenic models in in-vitro as well as in-vivo experimental system revealed the angio-regression mediated anticancer effect in lung cancer. These effects are due to the impeded expression of angiogenic mediators such as VEGF, MMP2&9 and inflammatory cytokines IL6 and TNFα to induce pathophysiological changes The study establishes new role of solanidine by targeting ATM/HIF-1α signaling to induce anti-angiogenesis for the first time. The study highlights the potentiality of plant based phytomedicine solanidine which can targets the multiple hallmarks of cancer by targeting interwoven signaling crosstalk. Such an approach through solanidine necessary to counteract heterogeneous complexity of cancer which could be nearly translated into drug.
    Keywords DNA damage ; DNA repair ; adenocarcinoma ; angiogenesis ; antineoplastic activity ; aorta ; apoptosis ; ascites ; comet assay ; cornea ; drugs ; gelatin ; gene expression ; hypoxia ; interleukin-6 ; lung neoplasms ; lungs ; models ; neoplasm cells ; oxygen ; phosphorylation ; rats ; solanidine ; therapeutics ; TME ; lung cancer ; DDR ; ATM/HIF ; anti-angiogenesis ; ATM ; BER ; Chk2 ; DNA DSB ; DAPI 4′ ; ELISA ; ECM ; HIF-1α ; HRE ; HR ; IL6 ; LLC ; MMP 2&9 ; MVD ; TNFα ; VEGF ; XRCC1
    Language English
    Dates of publication 2023-0718
    Publishing place Elsevier GmbH
    Document type Article ; Online
    Note Pre-press version
    ZDB-ID 1205240-1
    ISSN 1618-095X ; 0944-7113
    ISSN (online) 1618-095X
    ISSN 0944-7113
    DOI 10.1016/j.phymed.2023.154981
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4115: 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)

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  3. Article ; Online: Synthesis of coumarin analogs appended with quinoline and thiazole moiety and their apoptogenic role against murine ascitic carcinoma.

    Prashanth, T / Avin, B R Vijay / Thirusangu, Prabhu / Ranganatha, V Lakshmi / Prabhakar, B T / Sharath Chandra, J N Narendra / Khanum, Shaukath Ara

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

    2019  Volume 112, Page(s) 108707

    Abstract: The synthesis and antiproliferative effect of a series of quinoline and thiazole containing coumarin analogs 12a-d and 13a-f respectively, on mice leukemic cells was performed. The chemical structures of newly synthesized compounds were confirmed by IR, ...

    Abstract The synthesis and antiproliferative effect of a series of quinoline and thiazole containing coumarin analogs 12a-d and 13a-f respectively, on mice leukemic cells was performed. The chemical structures of newly synthesized compounds were confirmed by IR,
    MeSH term(s) Animals ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents/toxicity ; Apoptosis/drug effects ; Carcinoma, Ehrlich Tumor/drug therapy ; Carcinoma, Ehrlich Tumor/pathology ; Cell Line, Tumor ; Computer Simulation ; Coumarins/chemical synthesis ; Coumarins/chemistry ; Coumarins/therapeutic use ; Coumarins/toxicity ; Lethal Dose 50 ; Mice ; Quinolines/chemistry ; Structure-Activity Relationship ; Thiazoles/chemistry
    Chemical Substances Antineoplastic Agents ; Coumarins ; Quinolines ; Thiazoles ; quinoline (E66400VT9R)
    Language English
    Publishing date 2019-02-27
    Publishing country France
    Document type Journal Article
    ZDB-ID 392415-4
    ISSN 1950-6007 ; 0753-3322 ; 0300-0893
    ISSN (online) 1950-6007
    ISSN 0753-3322 ; 0300-0893
    DOI 10.1016/j.biopha.2019.108707
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.198: 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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