Antiproliferative and apoptotic effects of indole derivative, N-(2-hydroxy-5-nitrophenyl (4′-methylphenyl) methyl) indoline in breast cancer cells
Indoline derivatives functions as an inhibitors of epidermal growth factor receptor (EGFR) with the anticancer potential against various cancers. We aim to investigate anti-breast cancer effects and mechanism of action of novel indoline derivatives. Molecular docking of seven indoline derivates with...
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Published in | European journal of pharmacology Vol. 881; p. 173195 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier B.V
15.08.2020
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Subjects | |
Online Access | Get full text |
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Summary: | Indoline derivatives functions as an inhibitors of epidermal growth factor receptor (EGFR) with the anticancer potential against various cancers. We aim to investigate anti-breast cancer effects and mechanism of action of novel indoline derivatives. Molecular docking of seven indoline derivates with EGFR revealed, N-(2-hydroxy-5-nitrophenyl (4′-methylphenyl) methyl) indoline (HNPMI) as the top lead compound. RT-PCR analysis showed the downregulation of PI3K/S6K1 genes in breast cancer cells through the activation of EGFR with HNPMI. This compound found to have higher cytotoxicity than Cyclophosphamide, with the IC50 of 64.10 μM in MCF-7 and 119.99 μM in SkBr3 cells. HNPMI significantly reduced the cell proliferation of MCF-7 and SkBr3 cells, without affecting non-cancerous cells, H9C2. Induction of apoptosis was analyzed by Caspase-3 and -9, DNA fragmentation, AO/EtBr staining and flow cytometry assays. A fold change of 0.218- and 0.098- for caspase-3 and 0.478- and 0.269- for caspase-9 in MCF7 and SkBr3 cells was observed, respectively. Caspase mediated apoptosis caused DNA fragmentation in breast cancer cells upon HNPMI treatment. The structural elucidation of HNPMI by QSAR model and ADME-Tox suggests, a bi-molecular interaction of HNPMI-EGFR which is related to antiproliferative and apoptotic activity. The data concludes that, HNPMI-induced the apoptosis via EGFR signaling pathway in breast cancer cells. Thus, HNPMI might serve as a scaffold for developing a potential anti-breast cancer therapeutic agent.
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0014-2999 1879-0712 |
DOI: | 10.1016/j.ejphar.2020.173195 |