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    Chloroquine used in combination with chemotherapy synergistically suppresses growth and angiogenesis in vitro and in vivo
    (Int Inst Anticancer Research, 2018) Gürel-Gürevin, Ebru; Kıyan, Hülya Tuba; Esener, Osman Behzat Burak; Aydınlık, Şeyma; Üvez, Ayça; Ulukaya, Engin; Dimas, Konstantinos; Armutak, Elif İlkay
    Background: The inhibition of autophagy using pharmacological inhibitors such as chloroquine may be an effective strategy to overcome chemotherapy or resistance to anti-angiogenic therapy. Materials and Methods: The cytotoxic effect of doxorubicin (0.1-1 mu M), chloroquine (0.25-32 ,mu M) and their combination were investigated by employing ATP assay in human umbilical vein endothelial cells (HUVECs). The effect of doxorubicin and chloroquine combination was also measured using tube formation assay on Matrigel. The anti-angiogenic activities of doxorubicin (2.5 mu g/pellet) and chloroquine (15 mu g/pellet), their combination, and standards (50 mu g/pellet) were tested in vivo using the chick embryo chorioallantoic membrane (CAM) assay. Results: The combination of doxorubicin and chloroquine significantly had a stronger anti-angiogenic effect than the positive control (+/-)-thalidomide and doxorubicin alone in the CAM assay and in vitro tube-formation assay. Conclusion: Chloroquine enhanced the anti-angiogenic effect of doxorubicin on CAM at the tested concentrations.
  • Küçük Resim Yok
    Öğe
    A Comparative Study on In vitro Anti-cancer and In vivo Anti-angiogenic Effects of TRPC Blockers Pyr-3 and SKF-96365
    (Bentham Science Publ Ltd, 2023) Kiyan, Hulya Tuba; Uvez, Ayca; Erkisa, Merve; Ikitimur-Armutak, Elif Ilkay; Yilmazer, Nadim; Esener, Osman Behzat Burak; Kutucu, Deniz Erol
    Introduction Angiogenesis is involved in many physiological and pathological conditions including cancer. A number of TRP channels induce angiogenesis, promote cell proliferation or induce apoptosis in several types of human cancers. Therefore, TRP channels may be considered potential pharmacological targets for therapeutic options of disorders caused by insufficient angiogenesis or aberrant vascularization. Aims This study aimed to comparatively investigate in vitro anti-cancer and in vivo anti-angiogenic effects of TRPC blockers Pyr-3 and SKF-96365. Methods For anti-cancer effects, four cancer cell lines (MDA-MB-231, A549, PC-3, and HCT-116) were used. In vivo anti-angiogenic effects were investigated by employing in vivo CAM assay of fertilized hen eggs. Results Pyr-3 affected cell viability in a dose-dependent manner, all concentrations of SKF-96365 significantly reduced cell viability in all cell lines. Pyr-3 and SKF-96365 at concentrations of 2.5 & mu;g/pellet and 50 & mu;g/pellet, respectively inhibited in vivo angiogenesis significantly. Conclusion The concentration of 2.5 & mu;g/pellet caused no irritation, whereas 50 & mu;g/pellet produced some slight irritation. Apart from their anti-cancer effects, our findings indicate that Pyr-3 and SKF-96365 may be promising anti-angiogenic agents for the treatment of angiogenesis-related disorders.