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The apoptotic effect of D Rhamnose ?-hederin, a novel oleanane-type triterpenoid saponin on breast cancer cells.

ABSTRACT: There is growing interest in development of natural products as anti-cancer and chemopreventive agents. Many triterpenoids have been proved as potential agents for chemoprevention and therapy of breast cancer. Ginsenosides from ginseng, which mostly belong to dammarane-type triterpenoids, have gained great attention for their anti-breast cancer activity with diverse mechanisms. However, studies of other kinds of triterpenoid saponins on breast cancer are limited. Previously, we purified and identified a novel oleanane-type triterpene saponin named D Rhamnose ?-hederin (DR?-H) from Clematis ganpiniana, a Chinese traditional anti-tumor herb. In the present study, DR?-H showed strong inhibitory activity on the growth of various breast cancer cells and induced apoptosis in these cells. DR?-H inhibited PI3K/AKT and activated ERK signaling pathway. PI3K inhibitor LY294002 synergistically enhanced DR?-H-induced apoptosis whereas MEK inhibitor U0126 reduced the apoptosis rate. Moreover, DR?-H regulated the ratio of pro-apoptotic and anti-apoptotic Bcl-2 family proteins. Furthermore, DR?-H induced depolarization of mitochondrial membrane potential which released Apaf-1 and Cytochrome C from the inter membrane space into the cytosol, where they promoted caspase-9 and caspase-3 activation. This is the first report on the pro-apoptotic effects of DR?-H, a novel oleanane-type triterpenoid saponin, on breast cancer cells and its comprehensive apoptosis pathways. It implied that oleanane-type triterpenoid saponin DR?-H could be a promising candidate for chemotherapy of breast cancer.

SUBMITTER: Cheng L

PROVIDER: S-EPMC3946269 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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The apoptotic effect of D Rhamnose β-hederin, a novel oleanane-type triterpenoid saponin on breast cancer cells.

Cheng Lin L Xia Tian-Song TS Wang Yi-Fen YF Zhou Wenbin W Liang Xiu-Qing XQ Xue Jin-Qiu JQ Shi Liang L Wang Ying Y Ding Qiang Q

PloS one 20140306 6

There is growing interest in development of natural products as anti-cancer and chemopreventive agents. Many triterpenoids have been proved as potential agents for chemoprevention and therapy of breast cancer. Ginsenosides from ginseng, which mostly belong to dammarane-type triterpenoids, have gained great attention for their anti-breast cancer activity with diverse mechanisms. However, studies of other kinds of triterpenoid saponins on breast cancer are limited. Previously, we purified and iden ...[more]

PMID: 24603880

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Project description:Natural product studies explore potential and interesting new compounds to discover innovative drugs. Nigella sativa (N. sativa) (Ranunculaceae) is traditionally used to treat diabetes. Flavonoids and triterpenoid mostly show anti-diabetic activity. The current study aim to identify new compounds by a systematic study of the anti-oxidant and anti-diabetic activity of aerial parts of N. sativa concerning. Phytochemicals were isolated from the methanolic extract of aerial parts of the plant by column chromatography and identified by nuclear magnetic resonance spectroscopy and mass spectroscopy. A new triterpenoid saponin glycoside was isolated along with flavonoids. The anti-diabetic study was carried out by DPPH, ABTS, α -glucosidase, and protein tyrosine phosphatase 1B assays at doses of 12.5 to 250 µM. The isolated phytochemicals were identified as 3-O-(β-d-xylopyranosyl-(1-3)-α-l-rhamnopyrnaosyl-(1-2)-α-l-arabinopyranosyl]-28-O-(α-l-rhamno-pyranosyl-(1-4)-β-d-glucopyranosyl-(1-6)-β-d-glucopyranosyl] hederagenin (1), flaccidoside III (2), catechol (3), quercetin-3-gentiobiosides (4), magnoflorine (5), nigelflavonoside B (6), nigelloside (7), quercetin sphorotrioside (8), kaempferol-3, 7-diglucoside (9), kaempferol 3-O-rutinoside (10), rutin (11), 3-O-[α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranpsylhederagenin (12), 3β,23,28-trihydroxyolean-12-ene-3-O-α-l-arabinopyranoside(1→4)-a-rhamnopyranosyl,(1→4)-β-d-gluco-pyranoside (13), 3-O-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranpsyl]-28-O-β-d-gluco-pyranosyl hederagenin (14), and α-hederin (15). These were isolated and are reported for the first time in this study. Compared 13 was identified as a new compound. Compound 2 was isolated for first time from the genus Nigella. Compound 6 was found to be the most active in the DPPH, and ABTS assays and compound 10 was found to be the most active in the α-glucosidase assay, with IC50 32.7 ± 0.1, 95.18 ± 0.9, 214.5 ± 0.0 µΜ, respectively. Compound 12, at a dose of 125 µΜ, showed anti-diabetic activity in a PTP1B assay with IC50 91.30 ± 2.5 µΜ. In conclusion, the anti-diabetic activity of N. sativa is due to its flavonoids and TTSGs. Therefore, our studies suggest that the aerial parts of N. sativa are also a valuable and alternate source of valuable phytochemicals that could be used to develop anti-oxidant and anti-diabetic medicines.

Dataset Information

The apoptotic effect of D Rhamnose ?-hederin, a novel oleanane-type triterpenoid saponin on breast cancer cells.

Publications

The apoptotic effect of D Rhamnose β-hederin, a novel oleanane-type triterpenoid saponin on breast cancer cells.

Similar Datasets

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