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.

Oct 23, 2023

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 CC 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.

Copyright © 2023. Published by Elsevier B.V.

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ABOUT THE EXPERTS

Michael Hermann Kengne Kamdem,Stéphane Zingue,Timothy Grein,Sebastian Maxeiner,Jochen Rutz,Edwin Mpho Mmutlane,Dieudonné Njamen,Roman A Blaheta,Derek Tantoh Ndinteh
Michael Hermann Kengne Kamdem

Centre for Natural Product Research, Department of Chemical Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, 2028, South Africa; Research Center for Synthesis and Catalysis, Department of Chemical Sciences, University of Johannesburg-Kingsway Campus, Auckland Park, 2008, South Africa. Electronic address: michaelhermannkamdem@gmail.com.

Stéphane Zingue

Centre for Natural Product Research, Department of Chemical Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, 2028, South Africa; Department of Urology, University Hospital Frankfurt, Johann Wolfgang Goethe-University, D-60596, Frankfurt am Main, Germany; Department of Pharmacotoxicology and Pharmacokinetics, University of Yaounde 1, P.O. Box 1364, Yaounde, Cameroon. Electronic address: stephane.zingue@fmsb-uy1.cm.

Timothy Grein

Department of Urology and Pediatric Urology, University Medical Center Mainz, Johannes Gutenberg-Universität Mainz, D-55131, Mainz, Germany. Electronic address: Timothy.Grein@kgu.de.

Sebastian Maxeiner

Department of Urology and Pediatric Urology, University Medical Center Mainz, Johannes Gutenberg-Universität Mainz, D-55131, Mainz, Germany. Electronic address: SebastianMaxeiner@gmx.de.

Jochen Rutz

Department of Urology and Pediatric Urology, University Medical Center Mainz, Johannes Gutenberg-Universität Mainz, D-55131, Mainz, Germany. Electronic address: Jochen.Rutz@kgu.de.

Edwin Mpho Mmutlane

Centre for Natural Product Research, Department of Chemical Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, 2028, South Africa; Research Center for Synthesis and Catalysis, Department of Chemical Sciences, University of Johannesburg-Kingsway Campus, Auckland Park, 2008, South Africa. Electronic address: edwinm@uj.ac.za.

Dieudonné Njamen

Department of Animal Biology and Physiology, University of Yaoundé 1, P.O. Box 812, Yaounde, Cameroon. Electronic address: dnjamen@gmail.com.

Roman A Blaheta

Department of Urology and Pediatric Urology, University Medical Center Mainz, Johannes Gutenberg-Universität Mainz, D-55131, Mainz, Germany. Electronic address: roman.blaheta@unimedizin-mainz.de.

Derek Tantoh Ndinteh

Centre for Natural Product Research, Department of Chemical Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, 2028, South Africa; Research Center for Synthesis and Catalysis, Department of Chemical Sciences, University of Johannesburg-Kingsway Campus, Auckland Park, 2008, South Africa. Electronic address: dndinteh@uj.ac.za.