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从突尼斯萝卜中分离得到的 4-(甲基硫代)-3-丁烯基异硫氰酸酯的体外自由基清除、抗增殖和抗玉米赤霉烯酮细胞毒性作用。

In-vitro free radical scavenging, antiproliferative and anti-zearalenone cytotoxic effects of 4-(methylthio)-3-butenyl isothiocyanate from Tunisian Raphanus sativus.

机构信息

Laboratory of Immunology, Environmental Microbiology and Cancerology, Faculty of Sciences Bizerte, Zarzouna, Tunisia.

出版信息

J Pharm Pharmacol. 2010 Feb;62(2):231-9. doi: 10.1211/jpp.62.02.0011.

DOI:10.1211/jpp.62.02.0011
PMID:20487203
Abstract

OBJECTIVES

The aim of this study was to investigate the antiradical and antioxidant properties of 4-(methylthio)-3-butenyl isothiocyanate (MTBITC) extracted from Raphanus sativus and to assess the effects of MTBITC on tumour cell growth, cytotoxicity induced by zearalenone, an oestrogenic mycotoxin, and modulation of the expression of the genes involved in these aspects of cell behaviour.

METHODS

A murine leukaemia cell line (L1210) was grown in vitro and supplemented with MTBITC (2, 4, 8, 16 and 32 microm) for 48 h. Cell growth was evaluated by the MTT assay. The chemopreventive role of MTBITC on the cytotoxic effect of zearalenone in a Balb/c mice keratinocyte cell line (C5-O) was also evaluated. Apoptosis and lipid peroxidation were assessed, as well as the expression of genes involved following zearalenone treatment alone or in combination with MTBITC.

KEY FINDINGS

MTBITC showed a significant ability to inhibit nitroblue tetrazolium reduction by superoxide radicals in a non-enzymatic superoxide generating system, to scavenge free radicals and to cause a decrease in L1210 cell growth. The C5-O cells treated with zearalenone alone showed a high frequency of apoptotic cells and lipid peroxidation, typical of oxidative stress generated by zearalenone. The cotreatment with MTBITC reduced the cytotoxicity of zearalenone and the subsequent gene expression analysis demonstrated that MTBITC decreased the expression of caspase 8, implicated in the physiological mechanism to eliminate injured or abnormal cells.

CONCLUSIONS

The results suggest that MTBITC was able to inhibit L1210 cell growth and counteract the zearalenone oxidative stress to C5-O cells through caspase 8 inhibition of apoptosis.

摘要

目的

本研究旨在探讨从萝卜中提取的 4-(甲基硫代)-3-丁烯基异硫氰酸酯(MTBITC)的抗氧化和清除自由基特性,并评估 MTBITC 对肿瘤细胞生长的影响、玉米赤霉烯酮(一种雌激素真菌毒素)诱导的细胞毒性以及对参与这些细胞行为方面的基因表达的调节作用。

方法

体外培养小鼠白血病细胞系(L1210),并添加 2、4、8、16 和 32μM 的 MTBITC 培养 48 小时。通过 MTT 法评估细胞生长。还评估了 MTBITC 在 Balb/c 小鼠角质细胞系(C5-O)中对玉米赤霉烯酮细胞毒性的化学预防作用。评估了细胞凋亡和脂质过氧化作用,以及玉米赤霉烯酮单独或与 MTBITC 联合处理后相关基因的表达。

主要发现

MTBITC 在非酶超氧自由基生成系统中对硝基蓝四唑还原具有显著的抑制超氧自由基的能力,可清除自由基并降低 L1210 细胞生长。单独用玉米赤霉烯酮处理的 C5-O 细胞显示出高频率的凋亡细胞和脂质过氧化,这是玉米赤霉烯酮产生的氧化应激的典型特征。与 MTBITC 共同处理可降低玉米赤霉烯酮的细胞毒性,随后的基因表达分析表明,MTBITC 降低了参与清除受损或异常细胞的生理机制中的半胱天冬酶 8 的表达。

结论

结果表明,MTBITC 能够抑制 L1210 细胞生长,并通过抑制半胱天冬酶 8 诱导的细胞凋亡来拮抗玉米赤霉烯酮对 C5-O 细胞的氧化应激。

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