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.