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可可茶(Camellia ptilophylla)通过凋亡对人肝癌 HepG2 细胞的体外和体内抑制作用。

Inhibitory effects of cocoa tea (Camellia ptilophylla) in human hepatocellular carcinoma HepG2 in vitro and in vivo through apoptosis.

机构信息

Department of Biology, School of Life Science, Sun Yat-sen University, Guangzhou, China.

出版信息

J Nutr Biochem. 2012 Sep;23(9):1051-7. doi: 10.1016/j.jnutbio.2011.05.010. Epub 2011 Oct 20.

DOI:10.1016/j.jnutbio.2011.05.010
PMID:22018604
Abstract

Cocoa tea (Camellia ptilophylla), a naturally decaffeinated tea commonly consumed as a healthy beverage in southern China, has been recently found to be a potential candidate for the treatment of different diseases, including obesity and cancers. The present study aimed to evaluate the anti-liver cancer activities of green cocoa tea infusion (GCTI) in vitro and in vivo using human hepatocarcinoma cell line HepG2 cells and nude mice xenograft model. The apoptotic activities of GCTI were assessed using flow cytometry, Western blotting and immunohistochemical analysis. Our results showed that GCTI significantly inhibited the proliferation of HepG2 cells in a dose-dependent manner (IC₅₀ values=292 μg/ml at 72 h). GCTI induced HepG2 cells to undergo apoptosis, which was demonstrated by cell cycle analysis and annexin-V and propidium iodide staining. The caspase cascade was activated as shown by significant proteolytic cleavage of caspase-3 and PARP in GCTI-treated cells in a dose- and time-dependent manner. In addition, GCTI increased the expression of cell cycle inhibitory proteins (p21, p27 and p53) and the Bax-to-Bcl-2 ratio to induce apoptosis. The antiproliferative effect of GCTI was confirmed in HepG2 xenograft nude mice. The tumor growth was effectively inhibited by GCTI in a dose-dependent manner as indicated by the decrease in tumor volume and tumor weight after 4 weeks of treatment. Administration of GCTI increased terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and caspase-3-positive cells in the tumor section. In conclusion, these results revealed that GCTI may be a potential and promising agent of natural resource to treat liver cancer.

摘要

可可茶(Camellia ptilophylla)是一种天然无咖啡因的茶,在中国南方常被作为健康饮品饮用,最近被发现是治疗肥胖症和癌症等多种疾病的潜在候选药物。本研究旨在通过人肝癌细胞系 HepG2 细胞和裸鼠异种移植模型,体外和体内评估绿茶可可茶提取物(GCTI)的抗肝癌活性。通过流式细胞术、Western blot 和免疫组织化学分析评估 GCTI 的促凋亡活性。我们的结果表明,GCTI 以剂量依赖性方式显著抑制 HepG2 细胞的增殖(72 h 时 IC₅₀值为 292 μg/ml)。GCTI 诱导 HepG2 细胞发生凋亡,这通过细胞周期分析和 annexin-V 和碘化丙啶染色得到证实。随着 GCTI 处理细胞中 caspase 级联的激活,caspase-3 和 PARP 的显著蛋白水解裂解得到证实。此外,GCTI 增加细胞周期抑制蛋白(p21、p27 和 p53)的表达和 Bax/Bcl-2 比值以诱导细胞凋亡。GCTI 在 HepG2 异种移植裸鼠中的抗增殖作用得到了证实。GCTI 以剂量依赖性方式有效抑制肿瘤生长,4 周治疗后肿瘤体积和重量的减少表明了这一点。GCTI 给药增加了肿瘤切片中的末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记和 caspase-3 阳性细胞。总之,这些结果表明 GCTI 可能是一种有潜力和有前途的天然资源药物,可用于治疗肝癌。

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