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

Two steroidal saponins, tigogenin hexasaccharide-1 (TGHS-1, (25R)-5alpha-spirostan-3beta-yl 4-O-[2-0-[3-O-(alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl]-3-0-[4-0- (alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl]-beta-D-glucopyranosyl]-3-D- galactopyranoside) and tigogenin hexasaccharide-2 (TGHS-2,...

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Bibliographic Details
Published in:Canadian journal of physiology and pharmacology 2001-11, Vol.79 (11), p.953-958
Main Authors: CANDRA, Ellyawati, MATSUNAGA, Kimihiro, FUJIWARA, Hironori, MIMAKI, Yoshihiro, SASHIDA, Yutaka, YAMAKUNI, Tohru, OHIZUMI, Yasushi
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biological and medical sciences
Blotting, Western
Cell death
Cell Separation
Cells
DNA Fragmentation
Electrophoresis, Agar Gel
Flow Cytometry
General pharmacology
Leukemia L1210
Liliaceae
Medical sciences
Mice
Pharmacognosy. Homeopathy. Health food
Pharmacology. Drug treatments
Plant Structures
Saponins
Saponins - isolation & purification
Saponins - pharmacology
Spirostans - isolation & purification
Spirostans - pharmacology
Tumor Cells, Cultured
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Summary:Two steroidal saponins, tigogenin hexasaccharide-1 (TGHS-1, (25R)-5alpha-spirostan-3beta-yl 4-O-[2-0-[3-O-(alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl]-3-0-[4-0- (alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl]-beta-D-glucopyranosyl]-3-D- galactopyranoside) and tigogenin hexasaccharide-2 (TGHS-2, (25R)-5alpha-spirostan-3beta-yl 4-O-[2-0-[3-0-(beta-D-glucopyranosyl)-beta-D-glucopyranosyl]-3-0-[4-0- (alpha-L-rhamnopyranosyl)-beta-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 microM. The morphological observation revealed that TGHS-1 and TGHS-2 induced shrinkage in cell soma and chromatin condensation, suggesting apoptotic cell 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 compounds, cells with sub-G1 DNA content were detected by flow cytometric analysis, indicating that TGHS-1 and TGHS-2 (each EC50 value of 0.1 microM) are the most powerful apoptotic saponins known. These results suggest that TGHS-1 and TGHS-2 induce apoptotic cell death through caspase-3 activation.
ISSN:0008-4212
1205-7541
DOI:10.1139/cjpp-79-11-953