Antiproliferative and apoptotic effects of indole derivative, N-(2-hydroxy-5-nitrophenyl (4'-methylphenyl) methyl) indoline in breast cancer cells.
European journal of pharmacology
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 50 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.
Women & Children
Institute for Systems Biology
Palanivel, Suresh; Murugesan, Akshaya; Subramanian, Kumar; Yli-Harja, Olli; and Kandhavelu, Meenakshisundaram, "Antiproliferative and apoptotic effects of indole derivative, N-(2-hydroxy-5-nitrophenyl (4'-methylphenyl) methyl) indoline in breast cancer cells." (2020). Articles, Abstracts, and Reports. 3196.