School of Biological Sciences, Nanyang Technological University, Singapore, 639798, Singapore.
Shared Analytics, Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), Singapore, 138671, Singapore.
J Integr Plant Biol. 2023 Jun;65(6):1442-1466. doi: 10.1111/jipb.13469. Epub 2023 Apr 4.
Plants accumulate a vast array of secondary metabolites, which constitute a natural resource for pharmaceuticals. Oldenlandia corymbosa belongs to the Rubiaceae family, and has been used in traditional medicine to treat different diseases, including cancer. However, the active metabolites of the plant, their biosynthetic pathway and mode of action in cancer are unknown. To fill these gaps, we exposed this plant to eight different stress conditions and combined different omics data capturing gene expression, metabolic profiles, and anti-cancer activity. Our results show that O. corymbosa extracts are active against breast cancer cell lines and that ursolic acid is responsible for this activity. Moreover, we assembled a high-quality genome and uncovered two genes involved in the biosynthesis of ursolic acid. Finally, we also revealed that ursolic acid causes mitotic catastrophe in cancer cells and identified three high-confidence protein binding targets by Cellular Thermal Shift Assay (CETSA) and reverse docking. Altogether, these results constitute a valuable resource to further characterize the biosynthesis of active metabolites in the Oldenlandia group, while the mode of action of ursolic acid will allow us to further develop this valuable compound.
植物积累了大量的次生代谢产物，这些产物构成了药物的天然资源。地菍属于茜草科，已被传统医学用于治疗多种疾病，包括癌症。然而，该植物的活性代谢产物、其生物合成途径以及在癌症中的作用方式尚不清楚。为了填补这些空白，我们将该植物暴露于八种不同的胁迫条件下，并结合了不同的组学数据，以捕捉基因表达、代谢谱和抗癌活性。我们的结果表明，地菍提取物对乳腺癌细胞系具有活性，而熊果酸是其活性的原因。此外，我们组装了一个高质量的基因组，并发现了两个参与熊果酸生物合成的基因。最后，我们还通过细胞热转移分析（CETSA）和反向对接鉴定了三个与熊果酸结合的高可信度蛋白结合靶标，揭示了熊果酸在癌细胞中导致有丝分裂灾难的机制。总之，这些结果为进一步研究地菍属中活性代谢产物的生物合成提供了有价值的资源，而熊果酸的作用方式将使我们能够进一步开发这种有价值的化合物。
