Cornulacin: a new isoflavone from and its isolation, structure elucidation and cytotoxicity through EGFR-mediated apoptosis.

Chemical investigation of the methanolic extract of (Amaranthaceae), an annual wild herb collected from North Sinai, Egypt, yielded a new isoflavone cornulacin 1 and five known compounds: -feruloyltyramine 2, -feruloyl-3'-methoxytyramine 3, -caffeoyl tyramine 4, Cannabisin F 5 and (2a, 3a) lyciumamide D 6. Using MTT assay, the isolated compounds were evaluated for their cytotoxicity against pancreatic (Panc1) and ovarian (A2780) cancer cell lines. Compounds 1, 2, 3, and 4 exhibited promising cytotoxic activity against the tested cells, among which compound 1 (IC of 2.1 ± 0.21 μM) was the most active one against A2780 cells, whereas compound 2 (IC of 3.4 ± 0.11 μM) was the most effective compound against Panc1 cells. Accordingly, compound 1 was further investigated for its apoptotic induction in A2780 cancer cells using Annexin V/PI staining. Compound 1 significantly stimulated apoptotic ovarian A2780 cancer cells by 45.9-fold and arrested cell proliferation in the S-phase. Such activity was mediated through the upregulation of proapoptotic genes Bax; P53; and caspase 3, 8, and 9 besides the downregulation of the Bcl-2 gene, the anti-apoptotic one. Furthermore, molecular docking investigation demonstrated the strong binding affinity of compound 1 with EGFR active sites, which validated its experimental EGFR enzyme inhibition activity.