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红花木(Cratoxylum formosum (Jack) Dyer ssp. pruniflorum (Kurz) Gogel.)提取物通过 caspase 依赖性途径诱导人肝癌 HepG2 细胞凋亡。

Cratoxylum formosum (Jack) Dyer ssp. pruniflorum (Kurz) Gogel. (Hóng yá mù) extract induces apoptosis in human hepatocellular carcinoma HepG2 cells through caspase-dependent pathways.

机构信息

Center for Research and Development of Herbal Health Products (CRD-HHP), Khon Kaen University, Khon Kaen 40002, Thailand.

出版信息

Chin Med. 2014 Apr 7;9(1):12. doi: 10.1186/1749-8546-9-12.

Abstract

BACKGROUND

Cratoxylum formosum (Jack) Dyer ssp. pruniflorum (Kurz) Gogel. (Hóng yá mù) (CF) has been used for treatment of fever, cough, and peptic ulcer. Previously, a 50% ethanol-water extract from twigs of CF was shown highly selective in cytotoxicity against cancer cells. This study aims to investigate the molecular mechanisms underlying the apoptosis-inducing effect of CF.

METHODS

The cytotoxicity of CF was evaluated in the human hepatocellular carcinoma (HCC) HepG2 cell line in comparison with a non-cancerous African green monkey kidney epithelial cell line (Vero) by a neutral red assay. The apoptosis induction mechanisms were investigated through nuclear morphological changes, DNA fragmentation, mitochondrial membrane potential alterations, and caspase enzyme activities.

RESULTS

CF selectively induced HepG2 cell death compared with non-cancerous Vero cells. A 1.5-fold higher apoptotic effect compared with melphalan was induced by 120 μg/mL of the 50% ethanol-water extract of CF. The apoptotic cell death in HepG2 cells occurred via extrinsic and intrinsic caspase-dependent pathways in dose- and time-dependent manners by significantly increasing the activities of caspase 3/7, 8, and 9, decreasing the mitochondrial membrane potential, and causing apoptotic body formation and DNA fragmentation.

CONCLUSIONS

CF extract induced a caspase-dependent apoptosis in HepG2 cells.

摘要

背景

臭娘子(Cratoxylum formosum(Jack)Dyer ssp. pruniflorum(Kurz)Gogel.)(红牙木)(CF)被用于治疗发热、咳嗽和胃溃疡。此前,研究表明 CF 的树枝的 50%乙醇-水提取物对癌细胞具有高度选择性的细胞毒性。本研究旨在探讨 CF 诱导细胞凋亡的分子机制。

方法

通过中性红测定法,将 CF 的细胞毒性与非癌性非洲绿猴肾上皮细胞系(Vero)进行比较,评估其在人肝癌(HCC)HepG2 细胞系中的作用。通过核形态变化、DNA 片段化、线粒体膜电位改变和半胱天冬酶酶活性研究诱导细胞凋亡的机制。

结果

CF 选择性诱导 HepG2 细胞死亡,而非癌性 Vero 细胞。CF 的 50%乙醇-水提取物在 120μg/mL 时诱导的凋亡作用比美法仑高 1.5 倍。CF 提取物以剂量和时间依赖性方式通过显著增加 caspase 3/7、8 和 9 的活性、降低线粒体膜电位、导致凋亡小体形成和 DNA 片段化,通过外源性和内源性 caspase 依赖性途径诱导 HepG2 细胞的细胞凋亡。

结论

CF 提取物在 HepG2 细胞中诱导 caspase 依赖性细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19e5/3985586/7ec1f106b00a/1749-8546-9-12-1.jpg

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