AUTHOR=Moriasi Gervason , Ngugi Mathew , Mwitari Peter , Omwenga George 

TITLE=In vitro anti-prostate cancer efficacy and phytochemical composition of the dichloromethane and ethyl acetate leaf extracts of Vitex doniana (sweet)

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1483856

DOI=10.3389/fphar.2024.1483856

ISSN=1663-9812

ABSTRACT=<sec><title>Background</title><p>Prostate cancer is a significant global health concern, particularly among ageing male populations, with a disproportionately higher burden in sub-Saharan Africa. Conventional treatments, though effective, are costly and cause devastating side effects which limit their clinical benefits. Hence, this study evaluated the <italic>in vitro</italic> antiprostate cancer properties and secondary metabolites of dichloromethane and ethyl acetate lead extracts of <italic>Vitex doniana</italic> to explore safer and efficacious natural alternatives based on ethnomedicinal claims.</p></sec><sec><title>Methods</title><p>Phytochemical profiling was conducted using gas chromatography-mass spectrometry (GC-MS) analysis to identify secondary metabolites in the extracts. The cytotoxic effects of the extracts were determined through the MTT assay using Vero CCL-81 cells and DU-145 cells. The expression profile of the selected genes (<italic>ar, bcl2, caspase-3, cdk1</italic>, and <italic>p53</italic>) in DU-145 cells treated with the study extracts was investigated using RT-qPCR.</p></sec><sec><title>Results</title><p>GC-MS analysis revealed 10 secondary metabolites in the dichloromethane extract and 27 secondary metabolites in the ethyl acetate extract of <italic>V. doniana</italic> leaves, with the majority being sesquiterpenes, diterpenoids, and phytosterols. The dichloromethane and ethyl acetate leaf extracts of <italic>V. doniana</italic> exhibited low cytotoxicity against normal mammalian epithelial cells (Vero CCL-81), with CC<sub>50</sub> values of 1,238.85 μg/mL and 964.81 μg/mL, respectively. Besides, the ethyl acetate leaf extract of the studied plant demonstrated potent anti-prostate cancer activity against DU-145 cells, with an IC<sub>50</sub> of 35.68 μg/mL and a high selectivity index (SI) of 27.04. Likewise, the dichloromethane leaf extract of this plant displayed cytotoxic effects (IC<sub>50</sub>: 287.01 μg/mL) and a selectivity index of 4.32. The reference drug (Doxorubicin) showed a higher toxicity against Vero CCL-81(IC<sub>50</sub>: 0.41 μg/mL) and DU-145 (IC<sub>50</sub>: 0.28 μg/mL) cells and a lower selectivity index of 1.46. The DU-145 cells treated with the studied plant extracts exhibited notable upregulation of <italic>ar</italic> and <italic>bcl2</italic>, and normalization of <italic>caspase 3, cdk1</italic> and <italic>p53</italic> expression.</p></sec><sec><title>Conclusion</title><p>The studied plant extracts possess <italic>in vitro</italic> anti-prostate cancer properties and could be promising candidates for further preclinical studies aimed at developing novel botanical-based therapies for the management of prostate cancer.</p></sec>