Department of Life and Earth Sciences, Higher Teachers' Training College, University of Maroua, Maroua, Cameroon; Department of Applied Chemistry, Faculty of Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, 2028, South Africa; Department of Urology, University Hospital Frankfurt, D-60596, Frankfurt Am Main, Germany.
Centre for Research on Medicinal Plants and Traditional Medicine (CRPMT), Institute of Medical Research and Medicinal Plants Studies, Yaounde, Cameroon.
J Ethnopharmacol. 2020 Jan 30;247:112251. doi: 10.1016/j.jep.2019.112251. Epub 2019 Sep 24.
Crateva adansonii DC (Capparaceae) is a shrub used to treat tumors in Cameroon. In our previous reports, a Crateva adansonii dichloromethane-methanol (DCM/MeOH) extract was shown to prevent chemically induced tumors in Wistar rats.
To determine the bioactive principle of Crateva adansonii extract and to elucidate its underlying mechanism.
An activity-guided fractionation was realized using MTT assay. To investigate if the bioactive compound daucosterol (CA2) accounted for the previously observed anticancer effects of the C. adansonii extract, it was tested on cell growth, cell proliferation, cell cycle, cell death mechanism and cell migration. In addition, cell cycle- and apoptosis-regulating proteins were assessed by Western blotting.
Daucosterol (CA2), a steroid saponin, was identified as major anticancer principle of the C. adansonii extract. Daucosterol significantly inhibited LNCaP, DU145 and PC3 prostate carcinoma cell growth and proliferation at the optimal concentration of 1 μg/mL. It also significantly increased the number of late apoptotic (DU145) and apoptotic (PC3) cells. The number of cells in S phase increased in DU145, while the number of G0/G1 cells decreased. Cell cycle proteins (cdk1, pcdk1, cyclin A and B) were down-regulated in DU145 and PC3 cells, whereas only cdk2 was down-regulated in PC3 cells. Moreover, the anti-apoptotic Akt, pAKT and Bcl-2 proteins were down-regulated, while the pro-apoptotic protein Bax was up-regulated. CA2 induced anti-metastatic effects by decreasing chemotaxis and cell migration, while it increased cell adhesion to fibronectin and collagen matrix.
These results suggest that daucosterol is the major active principle responsible at least in part for the anticancer effect of the extract of Crateva adansonii.
Crateva adansonii DC（山柑科）是一种灌木，用于治疗喀麦隆的肿瘤。在我们之前的报告中，已经表明 Crateva adansonii 的二氯甲烷-甲醇（DCM/MeOH）提取物可预防 Wistar 大鼠的化学诱导肿瘤。
确定 Crateva adansonii 提取物的生物活性成分，并阐明其潜在机制。
使用 MTT 测定法进行了活性导向的分段。为了研究生物活性化合物豆甾醇（CA2）是否归因于 Crateva adansonii 提取物先前观察到的抗癌作用，将其用于细胞生长、细胞增殖、细胞周期、细胞死亡机制和细胞迁移的测试。此外，通过 Western blotting 评估细胞周期和凋亡调节蛋白。
鉴定出豆甾醇（CA2），一种甾体皂苷，是 Crateva adansonii 提取物的主要抗癌成分。豆甾醇在最佳浓度 1μg/mL 时显著抑制 LNCaP、DU145 和 PC3 前列腺癌细胞的生长和增殖。它还显著增加晚期凋亡（DU145）和凋亡（PC3）细胞的数量。DU145 中 S 期细胞数量增加，而 G0/G1 细胞数量减少。DU145 和 PC3 细胞中的细胞周期蛋白（cdk1、pcdk1、cyclin A 和 B）下调，而仅在 PC3 细胞中下调 cdk2。此外，抗凋亡 Akt、pAKT 和 Bcl-2 蛋白下调，而促凋亡蛋白 Bax 上调。CA2 通过降低趋化性和细胞迁移来诱导抗转移作用，同时增加细胞对纤维连接蛋白和胶原蛋白基质的粘附。
这些结果表明，豆甾醇是负责提取物抗癌作用的主要活性成分之一。
