Department of Molecular Biology and Biotechnology, Pan African University Institute for Basic Sciences, Technology and Innovation, Nairobi, Kenya.
Department of Biochemistry, School of Biomedical Sciences, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya.
BMC Complement Med Ther. 2024 Sep 20;24(1):338. doi: 10.1186/s12906-024-04642-8.
Current prostate cancer treatments are associated with life-threatening side effects, prompting the search for effective and safer alternatives. Aspilia pluriseta Schweinf. ex Engl. has previously shown anticancer activity in lung and liver cancer cell lines. This study investigated its potential for prostate cancer.
A crude extract of A. pluriseta root was prepared using dichloromethane/methanol (1:1 v/v) and partitioned into hexane, ethyl acetate, and water fractions. The MTT assay was used to assess the antiproliferative activity of the fractions. The active fractions were tested at 6.25-200 µg/ml on human prostate cancer DU-145 cells and non-cancerous Vero E6 cells. Qualitative phytochemical and gas chromatography-mass spectrometry (GC-MS) analyses were conducted to identify chemical compounds. Network pharmacology was employed to predict molecular targets and modes of action of the identified chemical compounds, with subsequent validation through molecular docking and real-time PCR.
Active extracts included crude dichloromethane/methanol, hexane, and ethyl acetate fractions, inhibiting DU-145 cell proliferation with IC values of 16.94, 20.06, and 24.14 µg/ml, respectively. Selectivity indices were determined to be 6.04 (crude), 3.62 (hexane), and 6.68 (ethyl acetate). Identified phytochemicals comprised phenols, terpenoids, flavonoids, tannins, sterols, and saponins. GC-MS analysis revealed seventy-nine (79) compounds, with seven (7) meeting ideal drug candidate parameters; their hub gene targets included MAPK3, MAPK1, IL6, TP53, ESR1, PTGS2, MMP9, MDM2, AR, and MAP2K1, implicating regulation of PI3K/Akt, MAPK, and p53 signaling pathways as potential modes of action. Core compounds such as 1-heneicosanol, lanosterol, andrographolide, and retinoic acid exhibited strong binding activities, particularly lanosterol with MAPK21 (-9.7 kcal/mol), ESR1 (-8.9 kcal/mol), and MAPK3 (-8.8 kcal/mol). Treatment with A. pluriseta downregulated AR expression and upregulated p53, while also downregulating CDK1 and BCL-2 and upregulating caspase-3.
A. pluriseta extracts inhibited DU-145 cell growth without causing cellular toxicity, suggesting great potential for development as an anti-prostate cancer agent. However, further in vitro and in vivo experiments are recommended.
目前的前列腺癌治疗方法存在危及生命的副作用，因此需要寻找有效且更安全的替代方法。Aspilia pluriseta Schweinf. ex Engl. 先前已显示出在肺癌和肝癌细胞系中具有抗癌活性。本研究调查了其在前列腺癌中的潜力。
使用二氯甲烷/甲醇（1:1 v/v）从 Aspilia pluriseta 根中制备粗提取物，并将其分为己烷、乙酸乙酯和水馏分。使用 MTT 测定法评估馏分的抗增殖活性。将活性馏分以 6.25-200 µg/ml 的浓度测试于人前列腺癌 DU-145 细胞和非癌细胞 Vero E6 细胞上。进行定性植物化学和气相色谱-质谱（GC-MS）分析以鉴定化合物。采用网络药理学预测鉴定出的化学化合物的分子靶标和作用模式，并通过分子对接和实时 PCR 进行验证。
活性提取物包括粗二氯甲烷/甲醇、己烷和乙酸乙酯馏分，对 DU-145 细胞增殖的 IC 值分别为 16.94、20.06 和 24.14 µg/ml。选择性指数分别为 6.04（粗）、3.62（己烷）和 6.68（乙酸乙酯）。鉴定出的植物化学物质包括酚类、萜类、类黄酮、单宁、甾醇和皂苷。GC-MS 分析显示有七十九（79）种化合物，其中七种（7）符合理想药物候选物参数；它们的关键基因靶标包括 MAPK3、MAPK1、IL6、TP53、ESR1、PTGS2、MMP9、MDM2、AR 和 MAP2K1，提示调节 PI3K/Akt、MAPK 和 p53 信号通路可能是其作用模式之一。核心化合物如 1-二十一烷醇、羊毛甾醇、穿心莲内酯和维甲酸表现出很强的结合活性，尤其是羊毛甾醇与 MAPK21（-9.7 kcal/mol）、ESR1（-8.9 kcal/mol）和 MAPK3（-8.8 kcal/mol）。Aspilia pluriseta 处理下调 AR 表达并上调 p53，同时下调 CDK1 和 BCL-2 并上调 caspase-3。
Aspilia pluriseta 提取物抑制 DU-145 细胞生长而不引起细胞毒性，表明其作为抗前列腺癌药物具有很大的潜力。但是，建议进一步进行体外和体内实验。
