Abstract

Saponins are well known as plant stress-induced protective agents. Saponin compounds are also considered responsible for numerous pharmacological properties including anticarcinogenic activity. This paper evaluates the antiproliferative activity and mode of action of spirostane (SAP-1016 and SAP-884) and furostane (KE-1046 and KE-1064) saponins we have isolated from Balanites aegyptiaca Del. The compound SAP-1016 (3β-O-β- d-xylopyranosyl-(1–3)-β- d-glucopyranosyl-(1–4)-[α- l-rhamnopyranosyl-(1–2)]-β- d-glucopyranoside) showed potent antiproliferative activity against MCF-7 human breast cancer cells and HT-29 human colon cancer cells, with IC 50 values of 2.4 ± 0.35 and 3.3 ± 0.19 μM, respectively, compared with dioscin, one of the most potent cytotoxic spirostane saponins, with IC 50 values of 3.1 ± 0.39 and 4.9 ± 0.32 μM, respectively. Significant anti-proliferative activity of SAP-1016 was also observed compared to a well-known anticancer agent, cisplatin, against both MCF-7 human breast cancer cells and HT-29 human colon cancer cells. Additionally, significant selectivity of growth inhibition, between MCF-7 breast cancer cells and HFF normal cells, was detected with the furostane saponins. Treatments of HT-29 cells with 5 μM SAP-1016 for 24 h generated caspase-3 cleavage and therefore apoptosis activation. SAP-1016 also demonstrated reactive oxygen species (ROS) generation in both HT-29 and MCF-7 cancer cells in a time-dependent manner.

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