Abstract：
: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.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Palanivel S,Murugesan A,Subramanian K,Yli-Harja O,Kandhavelu Mdoi
10.1016/j.ejphar.2020.173195subject
Has Abstractpub_date
2020-08-15 00:00:00pages
173195eissn
0014-2999issn
1879-0712pii
S0014-2999(20)30287-9journal_volume
881pub_type
杂志文章abstract：:In urethane-chloralose anesthetised rats the muscle relaxant activity of flupirtine was investigated on the monosynaptic Hoffmann reflex recorded from plantar foot muscles and on the polysynaptic flexor reflex recorded from tibialis muscle. Intraperitoneal (i.p.; 2.5-25 mumol/kg) and intrathecal (i.t.; 33-330 nmol) ad...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00043-k
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abstract：:In this study the effect of purified rat anti-mouse IL-5 monoclonal antibody on aeroallergen-induced infiltration of eosinophils in the bronchoalveolar lavage fluid of guinea pigs was studied. The i.p. injection of anti-IL-5 antibody 4 h after aeroallergen challenge inhibited eosinophil infiltration in a dose-dependen...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
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doi：10.1016/j.ejphar.2006.08.012
更新日期：2006-11-07 00:00:00
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journal_title：European journal of pharmacology
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doi：10.1016/0014-2999(92)90655-n
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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更新日期：1993-01-05 00:00:00
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journal_title：European journal of pharmacology
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doi：10.1016/j.ejphar.2019.04.039
更新日期：2019-07-15 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1988-02-16 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(80)90281-2
更新日期：1980-03-21 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2017.07.034
更新日期：2017-10-15 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.04.065
更新日期：2008-07-28 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1989-03-14 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.03.010
更新日期：2009-06-10 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)02360-9
更新日期：2002-10-18 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01513-8
更新日期：2001-12-14 00:00:00
abstract：:The relaxant actions of vasoactive intestinal peptide (VIP) and bethanechol were examined on ring segments of intrapulmonary artery (IPA) isolated from cat lung. On a molar basis, VIP was 75 times more potent than bethanechol; however, VIP was less efficacious than bethanechol in reversing phenylephrine induced tone. ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90039-0
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1992-03-31 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1980-06-27 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1987-03-17 00:00:00
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1991-07-09 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1995-11-14 00:00:00
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journal_title：European journal of pharmacology
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更新日期：2003-01-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.02.002
更新日期：2008-04-14 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01193-1
更新日期：2001-09-07 00:00:00
abstract：:Inhibition by antipsychotic drugs of voltage-gated L-type Ca2+ channels was characterized in rat neuronal cell line pheochromocytoma PC12 cells. Under whole-cell voltage-clamp, haloperidol and chlorpromazine (1-100 microM) inhibited Ba2+ current permeating through Ca2+ channels. Fluspirilene and pimozide the Ba2+ curr...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1996-10-24 00:00:00
abstract：:We have developed an isolated spinal cord-skin preparation of the newborn rat. The spinal cord together with a piece of skin connected to the cord by the saphenous nerve was isolated from 1- to 4-day-old rats and separately superfused with artificial cerebrospinal fluid in two neighbouring chambers. Potentials were re...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90737-o
更新日期：1992-09-22 00:00:00
