Attività biologica di metaboliti secondari da Passiflora palmeri su linee tumorali umane

The genus Passiflora, comprising several hundred species that are indigenous to the tropical and semi-tropical areas of America, is well known in traditional medicine for its therapeutics properties. This feature, together with the observations of the interaction of the plants with their environment and the available chemotaxonomic information, makes the genus Passiflora a potential source of natural molecules of pharmacological relevance. However, only a few species of this genus have been widely studied from a phytochemical point of view and the biological activity on human tumor cell lines has not been investigated yet. In the first part of this work we searched for species with potential antitumor activity, focusing on molecular mechanisms involved. Preliminary screening on MDA-MB-231 cell line showed that P. palmeri and P. foetida have the strongest cytotoxic activity. Moreover, methanolic extract from leaves of P. palmeri kills tumoral cells in a selective manner, with a weak effect on normal fibroblasts; the apoptotic pathway is involved in the observed cell death. In order to give a phytochemical characterization and to identify the compounds responsible for the cytotoxic activity, in the second part of this work we analyzed the composition of secondary metabolites from active extracts. For this purpose, we combined a classical ‘bioguided’ approach with a ‘metabolomic’ approach that included a wider analysis of metabolites from the methanolic extracts. By applying principal component analysis (PCA) to LC-ESI-MS data from active and non active extracts, we identified the molecules that significantly contribute to the separation of the two types of extracts. The analysis of the active extracts revealed the presence of several apigenin and luteolin derivatives. By comparison with available commercial standards we confirmed the presence of luteolin, vitexin, luteolin 7-O-glucoside and apigenin 7-O-glucoside. The two different approaches (‘bioguided’ and ‘metabolomic’) employed have produced comparable results, even if it was not possible to find in the extracts any components that could exhaustively explain its cytotoxic activity. However we identified some molecules (i.e. apigenin, luteolin and chrysoeriol) that can contribute to this activity by acting specifically against tumoral cells, in line with previous observation on total extract. Since one of the goals of modern cancer therapy is to increase the selectivity of antitumor drugs, we can conclude that methanolic extract from leaves of P. palmeri is a possible source of compounds for the development of selective anticancer drugs.