Aridanin and oleanane-3- O-β-D-glucoside-2′-acetamide obtained from Tetrapleura tetraptera (Schumach. & Thonn) Taub. (Fabaceae) induces potent apoptotic activity in human prostate cancer cells

Tetrapleura tetraptera (Schumach. and Thonn.) Taub. (Fabaceae) is a tropical plant that is used in Cameroon pharmacopeia for the treatment of many cancers including prostate cancer (PCa), which is a major cause of men's death worldwide. The objective of this study was to evaluate the anticancer properties as well as underlying mechanisms of isolates from T. tetraptera on DU145, PC3 and LNCaP cancer cell lines. Eight (8) compounds were purified from T. tetraptera stem bark extract through silica gel column chromatography (CC) and characterized using spectroscopic techniques (1D and 2D NMR), HRESIMS. Cell growth was assessed by a well-characterized MTT assay, while BrdU and clonogenicity assays provided information on the cell proliferation index. Further, the impact of the compounds on cell cycle progression and cell death were performed through Flow cytometry. Cell adhesion, cell migration and chemotaxis along with some proteins of epithelial-mesenchymal transition (EMT) were assayed. Out of the eight (1–8) isolates from T. tetraptera only oleanane-3-O-β-D-glucoside-2′-acetamide and aridanin showed potent cell growth arrest with an estimated CC50 of 15, 23, 16 and 17, 26, 16 μg/mL on DU145, PC3 and LNCaP cells, respectively. A 15% (DU145) and 25% (LNCaP) increase in apoptotic cells induced by oleanane-3-O-β-D-glucoside-2′-acetamide and aridanin at 10 μg/mL were noticed. Oleanane-3-O-β-D-glucoside-2′-acetamide and aridanin at 2.5 and 10 μg/mL reduced the number of cells in S-phase and raised cells in G2/M phase. At the same concentrations, they decreased the number of invading DU145 cells and increased the adherence of DU145 cells to fibronectin and collagen matrix at tested concentrations, accompanied by an increase in integrin β-1 (10 μg/mL) and integrin β-4 (2.5 μg/mL) expression. Furthermore, a down-regulation of pcdk1, cdk2, Bcl-2, N-Cad, vimentin and cytokeratine 8–18 was noticed while, p19, p27, p53 pAKT, Bax, caspase-3 and E-Cad were up-regulated. This study outlines for the first time, the anticancer ability of compounds oleanane-3-O-β-D-glucoside-2′-acetamide (4) and aridanin (6) from Tetrapleura tetraptera and proposes their putative mechanisms of action. [Display omitted]