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 ...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.展开更多
基金supported by Nanyang Biologics,M.M.is supported by a NTU Start-Up Grant and Singaporean Ministry of Education grant MOE2018-T2-2-053.J.M.D(NTU-PPF-2019)supported by Natural Product Research Laboratory Biomedical Research Council of A^(*)STAR(Agency for Science,Technology and Research)Transition Fund(H16/99/b0/004)the Singapore Institute of Food and Biotechnology Innovation core fund。
文摘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.
