Background: Saponins from Medicago species display several biological activities, among them
apoptotic effects against plant cells have been evidenced. In contrast, their cytotoxic and antitumor activity
against animal cells have not been studied in great details.
Objective: To explore the cytotoxic properties of saponin from Medicago species against animal cells and their
effect in combination with the antitumoral drug cisplatin.
Method: Cytotoxic activity of saponin mixtures from M. arabica (tops and roots), M. arborea (tops) and M.
sativa (tops, roots and seeds) and related prosapogenins from M. arborea and M. sativa (tops) against HeLa and
MCF-7 cell lines is described. In addition, cytotoxicity of soyasaponin I and purified saponins (1-8) of hederagenin,
medicagenic and zanhic acid is also presented. Combination experiments with cisplatin have been also
Results: Saponins from M. arabica tops and roots (mainly monodesmosides of hederagenin and bayogenin)
were the most effective to reduce proliferation of HeLa and MCF-7 cell lines. Among the purified saponins, the
most cytotoxic was saponin 1, 3-O-ß-D-glucopyranosyl(1→2)-α-L-arabinopyranosyl hederagenin. When saponins,
derived prosapogenins and pure saponins were used in combination with cisplatin, they all, to different
extent, were able to potentiate cisplatin activity against HeLa cells but not against MCF-7 cell lines. Moreover
uptake of cisplatin in these cell lines was significantly reduced.
Conclusion: Overall results showed that specific molecular types of saponins (hederagenin glycosides) have
potential as anti-cancer agents or as leads for anti-cancer agents. Moreover saponins from Medicago species
have evidenced interesting properties to mediate cisplatin effects in tumor cell lines.