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Two new steroidal saponins, 8 and 10, along with 7 known steroidal sapogenins and saponins (1-7) and a furostanol saponin (9) were isolated from Agave sisalana Perrine ex Engelm. The structures of these two new compounds were identified and characterized by 1D and 2D NMR spectroscopy and mass spectrometry. In addition, acid hydrolysis and GC-FID were used to confirm the sugar moieties of 8 and 10. The cytotoxic effects of 1-10 on MCF-7, NCI-H460, and SF-268 cancer cells were evaluated, and among them, compound 10 proved to be the most cytotoxic with IC50 values of 1.2, 3.8, and 1.5 μM, respectively. [ABSTRACT FROM AUTHOR]

Aqueous extracts ofSalvia miltiorrhizae Bunge have been extensively used in the treatment of cardiovascular disorders and cancer in Asia. Recently, a compound, 5-(3-hydroxypropyl)-7-methoxy-2-(3'-methoxy-4'-hydroxyphenyl)-3-benzo[b]furancarbaldehyde (salvinal), isolated from this plant showed inhibitory activity against tumor cell growth and induced apoptosis in human cancer cells. In the present study, we investigated the cytotoxic effect and mechanisms of action of salvinal in human cancer cell lines. Salvinal caused inhibition of cell growth (IC(50) range, 4-17 microM) in a variety of human cancer cell lines. Flow cytometry analysis showed that salvinal treatment resulted in a concentration-dependent accumulation of cells in the G(2)/M phase. We observed, using Hoechst 33258 dye staining, that salvinal blocked the cell cycle in mitosis. In vitro and in vivo examinations showed that salvinal inhibited tubulin polymerization in a concentration-dependent manner. Immunocytochemical studies demonstrated that salvinal treatment caused the changes of cellular microtubule network, similar to the effect of colchicine. In addition, salvinal treatment resulted in upregulation of cyclin B1 levels, activation of Cdc2 kinase, and Cdc25c phosphorylation. Furthermore, elevation of levels of MPM-2 phosphoepitopes in salvinal-treated cells in a concentration-dependent manner was also observed. Similar to the effect of other antitubulin agent, hyperphosphorylation of Bcl-2, induction of DNA fragmentation and activation of caspase-3 activity occurred in salvinal-treated cells. In particular, salvinal exhibited similar inhibitory activity against parental KB, P-glycoprotein-overexpressing KB vin10 and KB taxol-50 cells, and multidrug resistance-associated protein (MRP)-expressing etoposide-resistant KB 7D cells. Taken together, our data demonstrate that salvinal inhibits tubulin polymerization, arrests cell cycle at mitosis, and induces apoptosis. Notably, Salvinal is a poor substrate for transport by P-glycoprotein and MRP. Salvinal may be useful in the treatment of human cancers, particularly in patients with drug resistance.