New cyclic glycolipids from Silene succulenta promote in vitro MCF-7 breast carcinoma cell apoptosis by cell cycle arrest and in silico mitotic Mps1/TTK inhibition.

Abstract

In vitro anticancer screening of Silene succulenta Forssk. aerial parts (Caryophyllaceae) showed that the n-hexane fraction was a highly effective fraction against breast carcinoma cell lines (MCF-7) with IC50 = 15.5 μg mL-1. The bioactive-guided approach led to the isolation of two new cyclic glucolipids from the n-hexane fraction, identified as a 1,2'-cyclic ester of 11-oxy-(6'-O-acetyl-β-d-glucopyranosyl) behenic acid (1) as a C-11 epimeric mixture and 11(R)-oxy-(β-d-glucopyranosyl)-1,2'-cyclic ester of behenic acid (2). An in vitro cytotoxicity study showed the potential suppression of MCF-7 cells with IC50 values of 11.7 ± 0.04 and 6.6 ± 0.01 μg mL-1 for compounds 1 and 2, respectively, compared to doxorubicin (IC50 = 3.83 ± 0.01 μg mL-1). Accordingly, only cell cycle tracking for the most active compound (2) was assessed. The cell cycle investigation showed that compound 2 altered the cell cycle at G0/G1, S, and G2/M phases in MCF-7 treated cells. In addition, its powerful apoptotic ability resulted in a significant increase in the early and late stages of apoptosis. Moreover, molecular docking analysis, which was performed against the anticancer mitotic (or spindle assembly) checkpoint target Mps1 kinase, showed that the two new cyclic glycolipids (1 and 2) possess high binding affinity of -7.7 and - 7.6 kcal mol-1, respectively, compared to its ATP ligand. Overall, this report emphasizes that natural cyclic glycolipids can be used as potential antitumour breast cancer agents.