Jakubikova Jana, Bao Yongping, Sedlak Jan
Nutrition Division, Institute of Food Research, Norwich Research Park, Norwich, NR4 7UA, UK.
Anticancer Res. 2005 Sep-Oct;25(5):3375-86.
Isothiocyanates from cruciferous vegetables have been identified as potent anticancer agents in animal and human epidemiological studies. The present study compared the biological activities of six dietary isothiocyanates (ITCs), allyl-ITC (AITC), benzyl-ITC (BITC), phenethyl-ITC (PEITC), sulforaphane (SFN), erucin (ERN) and iberin (IBN), on cell cycle progression, apoptosis induction and mitochondrial transmembrane potential in multidrug-resistant HL60/ADR (MRP-1-positive) and HL60/VCR (Pgp-1-positive) cells in comparison to the parent cell line HL60. Multidrug-resistant HL60/ADR and HL60/VCR cells were less sensitive than the parental HL60 cells to all the six tested ITCs, since the medians of IC50 values were 2.8- and 2.0-fold higher. All the selected ITCs induced time- and dose-dependant G2/M arrest, with the most effective AITC (10 microM, 24 h) inducing 52% G2/M accumulation in HL60 cells. Apoptosis was determined by Annexin V-FITC staining, metabolic conversion of fluorescein diacetate and sub-G1 population quantification. Cell cycle distribution and mitochondrial JC-1 aggregation were determined by flow cytometry. The effectiveness of ITCs in apoptosis induction and mitochondrial potential dissipation followed the order: BITC=PEITC>ERN=IBN>AITC>SFN.
在动物和人类流行病学研究中，十字花科蔬菜中的异硫氰酸盐已被确认为强效抗癌剂。本研究比较了六种膳食异硫氰酸盐（ITC），即烯丙基异硫氰酸盐（AITC）、苄基异硫氰酸盐（BITC）、苯乙基异硫氰酸盐（PEITC）、萝卜硫素（SFN）、山嵛菜碱（ERN）和异白屈菜红碱（IBN），对多药耐药的HL60/ADR（MRP-1阳性）和HL60/VCR（Pgp-1阳性）细胞的细胞周期进程、凋亡诱导和线粒体跨膜电位的影响，并与亲本细胞系HL60进行比较。多药耐药的HL60/ADR和HL60/VCR细胞对所有六种测试的ITC的敏感性低于亲本HL60细胞，因为IC50值的中位数分别高2.8倍和2.0倍。所有选定的ITC均诱导时间和剂量依赖性的G2/M期阻滞，最有效的AITC（10 microM，24小时）在HL60细胞中诱导52%的G2/M期积累。通过膜联蛋白V-FITC染色、荧光素二乙酸酯的代谢转化和亚G1期群体定量来确定凋亡。通过流式细胞术确定细胞周期分布和线粒体JC-1聚集。ITC在诱导凋亡和线粒体电位耗散方面的有效性顺序为：BITC = PEITC>ERN = IBN>AITC>SFN。
