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Prospects of Wedelolactone as a Chemotherapeutic Agent in Gynecological Cancers; Clue From its In-vitro and In-silico Investigation

Author(s):

Sadia Sarwar*, Tauqeer Amed, NeelumGul Qazi, Jun Qing Yu and Fazlul Huq   Pages 1 - 11 ( 11 )

Abstract:


Identification or development of new drugs to be used singly or in combination 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 in estrogen dependent and independent multiple gynecological tumor models. Cytotoxicity of wedelolactone (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 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, alp topoisomerase II and dihydrofolatereductase playing pivotal roles in driving multiple tumors. 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: ERα >Braf kinases > topoisomerase > CDPK > aromatase > alkaline phosphatase >NFkB> EGCG > DHFR >braf kinases > topoisomerase > CDPK > aromatase >NFkB> ERα > Alkaline phosphatase. We identified wedelolactone as a cytotoxic agent in breast and ovarian tumor models with the potential to inhibit multiple targets in 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.

Keywords:

In-silico, Ovarian cancer, Epigallocatechingallate, wedelolactone, topoisomerase, phytochemicals, ER

Affiliation:

Discipline of Biomedical Sciences, Sydney Medical School, The University of Sydney, Cumberland campus, NSW, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Discipline of Biomedical Sciences, Sydney Medical School, The University of Sydney, Cumberland campus, NSW, Discipline of Biomedical Sciences, Sydney Medical School, The University of Sydney, Cumberland campus, NSW



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