Correlations between camptothecin and related metabolites in Camptotheca acuminata reveal similar biosynthetic principles and in planta synergistic effects.

Camptothecin (CPT), 9-methoxycamptothecin (9-MeO-CPT), and 10-hydroxycamptothecin (10-OH-CPT) are potent antineoplastic metabolites. We analyzed these metabolites in Camptotheca acuminata sampled from Germany and China, using LC-MS/MS and LC-ESI-HRMS/MS, coupled with chemometrics. Multivariate analysis revealed that fresh stems of C. acuminata from China had the highest comprehensive metabolite load. Significant positive correlations of CPT with 9-MeO-CPT and 10-OH-CPT were observed by Kruskal's multidimensional scaling and principal component analysis. Linear discriminant analysis and hierarchical agglomerative cluster analysis revealed that C. acuminata from China was separated from others. These positive correlations indicate that these metabolites are biosynthesized similarly and operate synergistically in planta.