Moriasi Gervason, Ngugi Mathew, Mwitari Peter, Omwenga George
Department of Biochemistry, Microbiology and Biotechnology, School of Pure and Applied Sciences, Kenyatta University, Nairobi, Kenya.
Department of Medical Biochemistry, School of Medicine, Mount Kenya University, Thika, Kenya.
Front Pharmacol. 2024 Nov 14;15:1483856. doi: 10.3389/fphar.2024.1483856. eCollection 2024.
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 antiprostate cancer properties and secondary metabolites of dichloromethane and ethyl acetate lead extracts of to explore safer and efficacious natural alternatives based on ethnomedicinal claims.
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 (, and ) in DU-145 cells treated with the study extracts was investigated using RT-qPCR.
GC-MS analysis revealed 10 secondary metabolites in the dichloromethane extract and 27 secondary metabolites in the ethyl acetate extract of leaves, with the majority being sesquiterpenes, diterpenoids, and phytosterols. The dichloromethane and ethyl acetate leaf extracts of exhibited low cytotoxicity against normal mammalian epithelial cells (Vero CCL-81), with CC 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 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: 287.01 μg/mL) and a selectivity index of 4.32. The reference drug (Doxorubicin) showed a higher toxicity against Vero CCL-81(IC: 0.41 μg/mL) and DU-145 (IC: 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 and , and normalization of and expression.
The studied plant extracts possess 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.
前列腺癌是一个重大的全球健康问题,在老年男性人群中尤为突出,在撒哈拉以南非洲地区的负担 disproportionately 更高。传统治疗方法虽然有效,但成本高昂且会导致严重的副作用,限制了其临床益处。因此,本研究评估了 dichloromethane 和乙酸乙酯铅提取物的抗前列腺癌特性和次生代谢产物,以根据民族医学主张探索更安全、有效的天然替代品。
使用气相色谱 - 质谱(GC - MS)分析进行植物化学剖析,以鉴定提取物中的次生代谢产物。通过使用 Vero CCL - 81 细胞和 DU - 145 细胞的 MTT 试验测定提取物的细胞毒性作用。使用 RT - qPCR 研究用研究提取物处理的 DU - 145 细胞中所选基因(,和)的表达谱。
GC - MS 分析显示 dichloromethane 提取物中有 10 种次生代谢产物,乙酸乙酯提取物中有 27 种次生代谢产物,其中大多数是倍半萜、二萜和植物甾醇。dichloromethane 和乙酸乙酯叶提取物对正常哺乳动物上皮细胞(Vero CCL - 81)表现出低细胞毒性,CC 值分别为 1,238.85 μg/mL 和 964.81 μg/mL。此外,所研究植物的乙酸乙酯叶提取物对 DU - 145 细胞显示出强大的抗前列腺癌活性,IC 为 35.68 μg/mL,选择性指数(SI)高,为 27.04。同样,该植物的 dichloromethane 叶提取物显示出细胞毒性作用(IC:287.01 μg/mL),选择性指数为 4.32。参考药物(阿霉素)对 Vero CCL - 81(IC:0.41 μg/mL)和 DU - 145(IC:0.28 μg/mL)细胞显示出更高的毒性,选择性指数较低,为 1.46。用研究植物提取物处理的 DU - 145 细胞表现出和的显著上调,以及和表达的正常化。
所研究的植物提取物具有抗前列腺癌特性,可能是进一步临床前研究的有前途的候选物,旨在开发基于植物的新型疗法用于前列腺癌的管理。
原文中“disproportionately”、“dichloromethane”等词未翻译完整,推测是原文录入有误,正常应完整翻译为“不成比例地”、“二氯甲烷”等,但按照要求未添加解释,保留了原文形式。