Two steroidal saponins from Camassia cusickii induce L1210 cell death through the apoptotic mechanism

Citation
E. Candra et al., Two steroidal saponins from Camassia cusickii induce L1210 cell death through the apoptotic mechanism, CAN J PHYSL, 79(11), 2001, pp. 953-958
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
ISSN journal
0008-4212 → ACNP
Volume
79
Issue
11
Year of publication
2001
Pages
953 - 958
Database
ISI
SICI code
0008-4212(200111)79:11<953:TSSFCC>2.0.ZU;2-Q
Abstract
Two steroidal saponins, tigogenin hexasaccharide-1 (TGHS-1, (25R)-5 alpha - spirostan-3 beta -yl 4-O-[2-O-[3-O- (alpha -L-rhamnopyranosyl)-beta -D-gluc opyranosyl]-3-O-[4-O-(alpha -L-rhamnopyranosyl)-beta -D-glucopyranosyl]-bet a -D-glucopyranosyl]-beta -D-galactopyranoside) and tigogenin hexasaccharid e-2 (TGHS-2, (25R)-5 alpha -spirostan-3 beta -yl 4-O-[2-O-[3-O- (beta -D-gl ucopyranosyl)-beta -D-glucopyranosyl]-3-O-[4-O-(alpha -L-rhamnopyranosyl)-b eta -D-glucopyranosyl]-beta -D-glucopyranosyl]-beta -D-galactopyranoside), were isolated from the fresh bulbs of Camassia cusickii. In murine leukemic L1210 cells, both compounds showed cytotoxicity with an EC50 value of 0.06 muM. The morphological observation revealed that TGHS-1 and TGHS-2 induced shrinkage in cell soma and chromatin condensation, suggesting apoptotic ce ll death. The cell death was confirmed to be apoptosis by Annexin V binding to phosphatidylserine in the cell membrane and excluding propidium iodide. A typical apoptotic DNA ladder and the cleavage of caspase-3 were observed after treatment with TGHS-1 and TGHS-2. In the presence of both the compou nds, cells with sub-G(1) DNA content were detected by flow cytometric analy sis, indicating that TGHS-1 and TGHS-2 (each EC50 value of 0.1 muM) are the most powerful apoptotic saponins known. These results suggest that TGHS-1 and TGHS-2 induce apoptotic cell death through caspase-3 activation.