Abstract:
BACKGROUND:Identification and development of new drug candidates to be used singly or in combination therapy is critical in anticancer research. In recent years, accumulating evidence encouraged us to investigate the anti-proliferative effects of a small and emerging phytochemical Wedelolactone (WDL) in estrogen-dependent and independent multiple gynecological tumor models. OBJECTIVE:The aim of this study was to investigate the growth inhibitory effect of WDL on estrogen- dependent and independent gynecological cell lines and to explore its inhibitory potential towards key targets through in silico study. METHODS:Cytotoxicity of WDL was investigated in human breast and ovarian cancer cell lines (MCF-7 and SKOV3) through 3-(4,5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay. Epigallocatechingallate (EGCG) was used as reference natural compound while cisplatin was taken as a standard clinical agent. Both WDL and EGCG in combination with cisplatin were also evaluated for their combined growth inhibitory potential in MCF-7 cells. WDL was also evaluated in silico against key factors including braf kinases, CDPK, ERα, aromatase, topoisomerase II and dihydrofolate reductase (DHFR) playing pivotal roles in driving multiple tumors. RESULTS AND DISCUSSION:The IC50 value of WDL was 25.77 ± 4.82 μM and 33.64 ± 1.45 μM in MCF-7 and SKOV-3 respectively. The binding energy order was as follows; WDL: DHFR >Braf kinases > CDPK; aromatase > topoisomerase II> ERα > NFkB > alkaline phosphatase; EGCG dihydrofolatereductase (DHFR) > aromatase >CDPK > topoisomerase II > braf kinases > alkaline phosphatase > CDPK > ERα > NFkB. CONCLUSION:We identified WDL as a cytotoxic agent in breast and ovarian tumor models with the potential to inhibit multiple targets in the oncogenic pathway including estrogen receptor ERα, as depicted through its in silico study. Based on our own research findings and from literature evidence, we conclude that further research should be encouraged to investigate different aspects of wedelolactone as an additional agent to be combined with antiestrogen/endocrine therapy.
journal_name
Curr Comput Aided Drug Desjournal_title
Current computer-aided drug designauthors
Sarwar S,Amed T,Qazi NG,Yu JQ,Huq Fdoi
10.2174/1573409915666191015113134subject
Has Abstractpub_date
2020-01-01 00:00:00pages
365-375issue
4eissn
1573-4099issn
1875-6697pii
CAD-EPUB-101458journal_volume
16pub_type
杂志文章abstract:BACKGROUND:Inhibition of penicillin binding protein 2A (PBP2A) represents a sound drug design strategy in combatting Methicillin resistant Staphylococcus aureus (MRSA). Considering the urgent need for effective antimicrobials in combatting MRSA infections, we have developed a statistically robust ensemble of molecular ...
journal_title:Current computer-aided drug design
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abstract:BACKGROUND:Gefitinib (lressa) is the most prescribed drug, highly effective to treat nonsmall cell lung cancer; primarily it was considered that targeted therapy is a kinase inhibitor. The nonsmall cell lung cancer is caused by mutation in the Epithelial Growth Factor Receptor (EGFR) gene. Iressa works by blocking the ...
journal_title:Current computer-aided drug design
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abstract:INTRODUCTION:Machine Learning is a useful tool for the prediction of cell-penetration compounds as drug candidates. MATERIALS AND METHODS:In this study, we developed a novel method for predicting Cell-Penetrating Peptides (CPPs) membrane penetrating capability. For this, we used orthogonal encoding to encode amino aci...
journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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abstract::PMD (p-menthane-3-8-diol) is an insect repellent that can be synthesized chemically or derived from a steam distillate residue of the leaves of lemon eucalyptus, Corymbia citriodora. It is one of the few natural product endorsed by the Center for Disease Control (USA) for topical application to protect against mosquit...
journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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journal_title:Current computer-aided drug design
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