Structure Elucidation of 16 Undescribed Steroidal Glycosides from the Underground Parts of Agapanthus africanus and Apoptosis-Inducing Activity in Small-Cell Lung Cancer Cell.

Abstract

To explore new candidates for anticancer agents from natural products, the underground parts of Agapanthus africanus, commonly used as an ornamental plant, were investigated phytochemically. As a result, 16 undescribed steroidal glycosides (1-16) were obtained, and their structures were determined mainly by NMR spectroscopic analysis and chemical transformations. The cytotoxic activities of the isolated compounds (1-16) against SBC-3 human small-cell lung cancer cells, A549 human adenocarcinoma cells, and HL-60 human promyelocytic leukemia cells were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2-tetrazolium bromide (MTT) assay. Compound 1, a bisdesmosidic furostanol glycoside, and 10, a bisdesmosidic spirostanol glycoside, were cytotoxic to all three cell lines with IC50 values ranging from 1.2 to 13 μM. As 1 exhibited the most potent cytotoxicity against SBC-3 cells among the isolated compounds, its apoptosis-inducing activity toward SBC-3 cells was examined. Compound 1 arrested SBC-3 cells at the G2/M phase of the cell cycle and effectively induced apoptosis via an intrinsic pathway accompanied by the dissipation of membrane potential and morphological changes in mitochondria.