Fagonia cretica inhibits proliferation of colorectal and prostate cancer cells through DNMT1 downregulation, oxidative stress induction, and ER-beta activation: An in Vitro and in silico study.

[ETHNOPHARMACOLOGICAL RELEVANCE] Fagonia cretica L. is a traditionally used medicinal plant in many cultures for the management of cancer and other ailments. However, systematic scientific evaluation of its anticancer efficacy and mechanisms remains limited.

[AIM OF THE STUDY] To investigate the antiproliferative effects and underlying molecular mechanisms of an ethanolic extract of Fagonia cretica against colorectal (HCT-116) and prostate (PC3) cancer cell lines.

[MATERIALS AND METHODS] The cytotoxic potential of F. cretica ethanolic extract was assessed by in vitro cell viability assays. Bioinformatics analyses and experimental validation were used to identify molecular targets and cellular pathways affected by the extract.

[RESULTS] The F. cretica extract exhibited potent antiproliferative activity in both colorectal and prostate cancer cell lines. Integrated in silico and experimental studies identified DNA methyltransferase 1 (DNMT1) as a principal molecular target of the plant's phytoconstituents. Treatment with the extract led to significant downregulation of DNMT1 at both protein and mRNA levels, accompanied by promotion of apoptosis and induction of oxidative stress. Furthermore, a marked upregulation of the tumor suppressor gene ER-β was observed following extract exposure. These dual actions, suppression of DNMT1 and activation of ER-β, appear central to the mechanism underlying the anticancer effects of F. cretica.

[CONCLUSION] Our study provides scientific validation for the ethnomedicinal use of Fagonia cretica as an anticancer agent. By targeting both epigenetic and apoptotic pathways, this plant extract offers promise as a natural therapeutic candidate for colorectal and prostate cancer management. Further studies are warranted to isolate active constituents and evaluate efficacy in vivo.