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• W4220715278 endingPage "174907" @default.
• W4220715278 startingPage "174907" @default.
• W4220715278 abstract "Over-expressions of epidermal growth factor receptor and vascular endothelial growth factor receptor were frequently associated with the metastasis of solid tumors. Vandetanib, a dual tyrosine kinase inhibitor of epidermal growth factor receptor and vascular endothelial growth factor receptor, was broadly effective in treating a variety of human solid tumors. The compelling evidence that hypoxia is involved in tumor resistance to cancer therapy. Hypoxia-inducible factor (HIF-1α), a major transcription factor in response to hypoxia, has been considered as a promising specific target for cancer therapy. We reported a stronger vandetanib derivative, compound 39, which was more potently decreased viability of A549, HT-29, MCF-7, HepG2, and HeLa cells than its parent compound vandetanib. Remarkable hypoxia-selectivity was observed in A549 cells (IC50 = 1.55 ± 0.23 μM under normoxia and 0.31 ± 0.06 μM under hypoxia, respectively) and HT-29 cells (IC50 = 12.89 ± 2.15 μM under normoxia and 3.47 ± 0.79 μM under hypoxia, respectively). The apoptosis of A549 and HT-29 cells induced by compound 39 were detected by flow cytometry. Western blot analysis demonstrated that compound 39 significantly down-regulated the anti-apoptotic B-cell lymphoma-2 (BCL-2) protein and up-regulated the expression of pro-apoptotic BCL2-Associated X (Bax) protein as well as promoted the cleavage of poly (ADP-ribose) polymerase PARP. HIF-1α was down-regulated by compound 39 in A549 and HT-29 cells under hypoxia. We also found that the depletion of intracellular Reduced Glutathione (GSH) as well as production of Reactive Oxygen Species (ROS) were critical for compound 39-mediated cell death." @default.
• W4220715278 created "2022-04-03" @default.
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• W4220715278 date "2022-05-01" @default.
• W4220715278 modified "2023-10-16" @default.
• W4220715278 title "Novel vandetanib derivative inhibited proliferation and promoted apoptosis of cancer cells under normoxia and hypoxia" @default.
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• W4220715278 doi "https://doi.org/10.1016/j.ejphar.2022.174907" @default.
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