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橙皮苷诱导肝母细胞瘤HepG2细胞发生类胀亡性细胞死亡:细胞外调节蛋白激酶1/2丝裂原活化蛋白激酶的参与[已修正]

hesperidin induces paraptosis like cell death in hepatoblastoma, HepG2 Cells: involvement of ERK1/2 MAPK [corrected].

作者信息

Yumnam Silvia, Park Hyeon Soo, Kim Mun Ki, Nagappan Arulkumar, Hong Gyeong Eun, Lee Ho Jeong, Lee Won Sup, Kim Eun Hee, Cho Jae Hyeon, Shin Sung Chul, Kim Gon Sup

机构信息

Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, Republic of Korea.

Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongnam Regional Cancer Center, Gyeongsang National University Hospital, Jinju, Republic of Korea.

出版信息

PLoS One. 2014 Jun 30;9(6):e101321. doi: 10.1371/journal.pone.0101321. eCollection 2014.

Abstract

Hesperidin, a natural flavonoid abundantly present in Citrus is known for its anti-cancer, anti-oxidant and anti-inflammatory properties. In this study we examined the effect of hesperidin on HepG2 cells. HepG2 cells treated with various concentration of hesperidin undergo a distinct type of programed cell death. Cytoplasmic vacuolization, mitochondria and endoplasmic reticulum swelling and uncondensed chromatin were observed in hesperidin treated cells. DNA electrophoresis show lack of DNA fragmentation and western blot analysis demonstrates lack of caspase activation and PARP cleavage. It was observed that hesperidin induced cell death is nonautophagic and also activate mitogen activated protein kinase ERK1/2. Taken together, the data indicate that hesperidin induces paraptosis like cell death in HepG2 cells with the activation of ERK1/2. Thus our finding suggests that hesperidin inducing paraptosis may offer an alternative tool in human liver carcinoma therapy.

摘要

橙皮苷是一种大量存在于柑橘类水果中的天然黄酮类化合物,以其抗癌、抗氧化和抗炎特性而闻名。在本研究中,我们检测了橙皮苷对肝癌细胞系HepG2细胞的影响。用不同浓度橙皮苷处理的HepG2细胞会经历一种独特类型的程序性细胞死亡。在经橙皮苷处理的细胞中观察到细胞质空泡化、线粒体和内质网肿胀以及染色质未凝聚。DNA电泳显示缺乏DNA片段化,蛋白质免疫印迹分析表明缺乏半胱天冬酶激活和聚(ADP-核糖)聚合酶(PARP)裂解。据观察,橙皮苷诱导的细胞死亡是非自噬性的,并且还激活丝裂原活化蛋白激酶ERK1/2。综上所述,数据表明橙皮苷通过激活ERK1/2在HepG2细胞中诱导类胀亡样细胞死亡。因此,我们的研究结果表明,橙皮苷诱导胀亡可能为人类肝癌治疗提供一种替代工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e864/4076305/a94f4294284a/pone.0101321.g001.jpg

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