11-羟基-15-氧代-贝壳杉-16-烯-19-酸诱导喉癌细胞死亡。

Induction of laryngeal cancer cell death by Ent-11-hydroxy-15-oxo-kaur-16-en-19-oic acid.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.

出版信息

Head Neck. 2010 Nov;32(11):1506-18. doi: 10.1002/hed.21357.

DOI:10.1002/hed.21357

PMID:20146336

Abstract

BACKGROUND

Ent-11-hydroxy-15-oxo-kaur-16-en-19-oic acid (5F) is known to exhibit antitumor activity, but its mechanism is not completely understood. 5F has not been tested in laryngeal cancer.

METHODS

Two laryngeal cancer cell lines were treated with 5F. Cell death was analyzed by MTT [3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyltetrazolium bromide] and Annexin V assay. Nuclear factor kappa beta (NF-κB)- and apoptosis-related molecules were examined.

RESULTS

5F induced laryngeal cancer cell death in a dose-dependent manner. The Annexin V assay and the measurement of cleavage of procaspase-3 and poly(ADP-ribose) polymerase demonstrated that the 5F-induced cell death was mainly apoptotic. 5F slightly reduced the basal level of NF-κB, but significantly suppressed the inducible NF-κB by reducing its transcriptional activity, protecting its inhibitory subunit IκBα from degradation, and suppressing its level in the nucleus. 5F also inhibited pro-proliferative and anti-apoptotic molecules but promoted pro-apoptotic Bax.

CONCLUSIONS

5F induces apoptosis of laryngeal cancer cells by inhibiting NF-κB activation/induction, suppressing pro-proliferative and anti-apoptotic molecules, and promoting pro-apoptotic Bax.

摘要

背景

已知 Ent-11-羟基-15-氧代-贝壳杉-16-烯-19-酸（5F）具有抗肿瘤活性，但作用机制尚不完全清楚。5F 尚未在喉癌中进行过测试。

方法

用 5F 处理两种喉癌细胞系。通过 MTT[3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐]和 Annexin V 分析检测细胞死亡。检测核因子 kappa beta（NF-κB）和凋亡相关分子。

结果

5F 以剂量依赖性方式诱导喉癌细胞死亡。Annexin V 分析和 caspase-3 前体及多聚（ADP-核糖）聚合酶的切割测量表明，5F 诱导的细胞死亡主要是凋亡。5F 轻度降低 NF-κB 的基础水平，但通过降低其转录活性、保护其抑制性亚基 IκBα 不被降解以及抑制其核内水平，显著抑制可诱导的 NF-κB。5F 还抑制促增殖和抗凋亡分子，但促进促凋亡 Bax。