Kuguaglycoside C, a constituent of Momordica charantia, induces caspase-independent cell death of neuroblastoma cells
Kuguaglycoside C, a constituent of Momordica charantia, induces caspase-independent cell death of neuroblastoma cells
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DOI：
10.1111/cas.12021
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发表时间：
2012-12-01
期刊：
影响因子：
5.7
通讯作者：
Suzuki, Takashi
中科院分区：
文献类型：
--
作者：
Tabata, Keiichi;Hamano, Aoi;Suzuki, Takashi
苦瓜糖苷 C 是从苦瓜叶中分离出来的一种三萜糖苷，该化合物的生物效应仍几乎未知。我们研究了苦瓜糖苷 C 对人神经母细胞瘤 IMR-32 细胞的抗癌作用。在MTT测定中，苦瓜糖苷C处理48小时后对IMR-32细胞产生显着的细胞毒性(IC50：12.6μM)。尽管Hoechst 33342染色检查显示苦瓜糖苷C在高浓度(100μM)下诱导核收缩，但在流式细胞术中未观察到凋亡小体。在有效浓度（30μM）的库瓜糖苷C下，未观察到caspase-3或caspase-9的激活。另一方面，该物质显着降低生存素和裂解聚（ADP-核糖）聚合酶（PARP）的表达。 Kuguaglycoside C 还显着增加凋亡诱导因子 (AIF) 的表达和裂解。此外，在双荧光细胞凋亡检测试验中，发现苦瓜糖苷 C 可以诱导不依赖于 caspase 的 DNA 切割。这些结果表明苦瓜糖苷 C 诱导不依赖半胱天冬酶的细胞死亡，并且至少部分参与细胞坏死性凋亡的机制。 （癌症科学 2012 年；103：2153-2158）
Kuguaglycoside C is a triterpene glycoside isolated from the leaves of Momordica charantia, and the biological effects of this compound remain almost unknown. We investigated the anti;?>cancer effect of kuguaglycoside C against human neuroblastoma IMR-32 cells. In the MTT assay, kuguaglycoside C induced significant cytotoxicity against the IMR-32 cells (IC50: 12.6 mu M) after 48h treatment. Although examination by Hoechst 33342 staining revealed that kuguaglycoside C induced nuclear shrinkage at a high concentration (100 mu M), no apoptotic bodies were observed on flow cytometry. No activation of caspase-3 or caspase-9 was observed at the effective concentration (30 mu M) of kuguaglycoside C. On the other hand, the substance significantly decreased the expression of survivin and cleaved poly (ADP-ribose) polymerase (PARP). Kuguaglycoside C also significantly increased the expression and cleavage of apoptosis-inducing factor (AIF). Moreover, kuguaglycoside C was found to induce caspase-independent DNA cleavage in the dual-fluorescence apoptosis detection assay. These results suggest that kuguaglycoside C induces caspase-independent cell death, and is involved, at least in part, in the mechanism underlying cell necroptosis. (Cancer Sci 2012; 103: 2153-2158)