Cytotoxic Activity and Metabolic Profiling of Fifteen Euphorbia Species

Abstract

Euphorbia is a large genus of flowering plants with a great diversity in metabolic pattern. Testing the cytotoxic potential of fifteen Euphorbia species revealed highest activity of E. officinarum L. against CACO2 cell line (IC₅₀ 7.2 µM) and of E. lactea Haw. against HepG2 and MCF-7 cell lines (IC₅₀ 5.2 and 5.1 µM, respectively). Additionally, metabolic profiling of the fifteen tested species, using LC-HRMS, for dereplication purposes, led to the annotation of 44 natural compounds. Among the annotated compounds, diterpenoids represent the major class. Dereplication approach and multivariate data analysis are adopted in order to annotate the compounds responsible for the detected cytotoxic activity. Results of PCA come in a great accordance with results of biological testing, which emphasized the cytotoxic properties of E. lactea Haw. A similarity correlation network showed that the two compounds with the molecular formula C₁₆H₁₈O₈ and C₂₀H₃₀O₁₀, are responsible for cytotoxic activity against MCF-7 and HepG2 cell lines. Similarly, the compound with molecular formula C₁₈H₃₅NO correlates with cytotoxic activity against CACO2.

Keywords: Euphorbia; LC-HRMS; PCA; cytotoxic activity; metabolic profiling.

Figure 1

Percentage of different classes of metabolites distributed in the tested 15 Euphorbia species.

Figure 2

(A): PCA score plot for all crude extracts of the tested Euphorbia species, (B): PCA loading plot showing the distinctive metabolites.

Figure 3

(A): The whole molecular network showing the clusters of different features. (B): extracted network showing the metabolites highly correlated to the cytotoxic activity against MCF-7 and HPEG2. Nodes are colored in pie chart and molecules grouped according to their concentration in the tested species. Edges are correlation values and the edge’s width is proportional with this value.

Figure 4

(A): OPLS-DA score plot showing a clear separation between (●) CACO2 cytotoxic extracts and (●) inactive ones, (B): S-loading plot showing the metabolites highly correlated with CACO2 cytotoxicity.