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杨梅花青素对人肝癌细胞凋亡的诱导及侵袭的抑制作用

Induction of apoptosis and inhibition of invasion in human hepatoma cells by anthocyanins from meoru.

作者信息

Shin Dong Yeok, Ryu Chung Ho, Lee Won Sup, Kim Dong Chul, Kim Seok Hyun, Hah Young-Sool, Lee Sung Joong, Shin Sung Chul, Kang Ho Sung, Choi Yung Hyun

机构信息

Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan, Korea.

出版信息

Ann N Y Acad Sci. 2009 Aug;1171:137-48. doi: 10.1111/j.1749-6632.2009.04689.x.

Abstract

Anthocyanins belong to a class of flavonoids exhibiting antioxidant and anti-inflammatory actions as well as a variety of chemotherapeutic effects. However, little is known about the cellular and molecular mechanism of anticancer activity. In this study, we investigated if the anthocyanins (delphinidin-3,5-diglucoside: cyanidin-3,5-diglucoside: petunidin-3,5-diglucoside: delphinidin-3-glucoside: malvdin-3,5-diglucoside: peonidin-3,5-diglucoside: cyanidin-3-glucoside: petunidin-3-glucoside: peonidin-3- glucoside: malvidin-3- glucoside = 27:63:8.27:1:2.21:2.21:6.7:1.25:5.72:1.25) [corrected] isolated from meoru (Vitis coignetiae Pulliat) exerted antiproliferative and anti-invasive and apoptotic effects on human hepatoma Hep3B cells. It was found that the anthocyanins could inhibit cell growth by 75% at the concentration of 400 microg/mL for 48 h. Flow cytometric analysis showed that the anthocyanins increased the amount of DNA fragments (sub-G1 fraction) in a dose-dependent manner, which is closely related to mitochondrial dysfunction and reduction in antiapoptotic proteins (Bcl-2, xIAP, cIAP-1, and cIAP-2). The anthocyanins also significantly inhibited the migration and invasion of Hep3B cells through a matrigel-coated chamber. Taken together this study indicates that the anthocyanins from meoru have antiproliferative and anti-invasive effects and may induce apoptosis through the activation of the mitochondrial pathway and inhibition of antiapoptotic proteins. This study provides evidence that the anthocyanins isolated from meoru might be useful in the treatment of human hepatitis B-associated hepatoma.

摘要

花青素属于一类黄酮类化合物,具有抗氧化、抗炎作用以及多种化疗效果。然而,关于其抗癌活性的细胞和分子机制却知之甚少。在本研究中,我们调查了从山葡萄(Vitis coignetiae Pulliat)中分离出的花青素(飞燕草素 - 3,5 - 二葡萄糖苷:矢车菊素 - 3,5 - 二葡萄糖苷:矮牵牛素 - 3,5 - 二葡萄糖苷:飞燕草素 - 3 - 葡萄糖苷:锦葵色素 - 3,5 - 二葡萄糖苷:芍药色素 - 3,5 - 二葡萄糖苷:矢车菊素 - 3 - 葡萄糖苷:矮牵牛素 - 3 - 葡萄糖苷:芍药色素 - 3 - 葡萄糖苷:锦葵色素 - 3 - 葡萄糖苷 = 27:63:8.27:1:2.21:2.21:6.7:1.25:5.72:1.25)[已校正]对人肝癌Hep3B细胞是否具有抗增殖、抗侵袭和凋亡作用。结果发现,花青素在浓度为400μg/mL作用48小时时可抑制细胞生长达75%。流式细胞术分析表明,花青素以剂量依赖的方式增加了DNA片段(亚G1期分数)的数量,这与线粒体功能障碍以及抗凋亡蛋白(Bcl - 2、XIAP、cIAP - 1和cIAP - 2)的减少密切相关。花青素还通过基质胶包被的小室显著抑制了Hep3B细胞的迁移和侵袭。综上所述,本研究表明山葡萄中的花青素具有抗增殖和抗侵袭作用,可能通过激活线粒体途径和抑制抗凋亡蛋白诱导细胞凋亡。本研究提供了证据,表明从山葡萄中分离出的花青素可能对治疗人类乙型肝炎相关肝癌有用。

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