Diallyl disulfide (DADS) induces the antitumorigenic NSAID-activated gene (NAG-1) by a p53-dependent mechanism in human colorectal HCT 116 cells
Diallyl disulfide (DADS) induces the antitumorigenic NSAID-activated gene (NAG-1) by a p53-dependent mechanism in human colorectal HCT 116 cells
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DOI：
10.1093/jn/132.4.773
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发表时间：
2002-04-01
影响因子：
4.2
通讯作者：
Eling, TE
中科院分区：
文献类型：
--
作者：
Bottone, FG;Baek, SJ;Eling, TE
大蒜作为一种抗癌剂是有吸引力的，因为它能够在体外诱导细胞凋亡，并在体内抑制动物肿瘤的形成和生长。二烯丙基二硫化物（DADS）是大蒜中抑制肿瘤细胞生长和诱导细胞凋亡的成分。我们研究了DADS对各种癌细胞系的影响，以更好地了解其对凋亡和凋亡相关基因的影响。非甾体抗炎药（NSAID）激活基因（NAG-1）具有促凋亡和抗肿瘤活性，并被抗癌药物如NSAID上调。在本研究中，将人结肠直肠HCT-116（野生型p53）、HCT-15（p53突变体）和人前列腺PC-3（p53突变体）细胞暴露于DADS。DADS在11.5和23 mumol/L时抑制所有细胞系中的细胞增殖，但在HCT-15和PC-3细胞中抑制程度较低。在HCT-116细胞中，DADS以剂量依赖性方式诱导p53和NAG-1，并且p53的诱导先于NAG-1的诱导。在HCT-116细胞中，NAG-1蛋白表达在4.6 mumol/L时增加2.4倍0.6，在23 mumol/L DADS时增加6.1倍+/- 1.7，而p53被诱导1.5倍+/- 0.1和2.3倍+/- 0.4。在p53突变细胞系中，DADS不诱导NAG-1或p53;然而，NAG-1表达被舒林酸硫化物诱导。用4.6和23 mumol/L DADS处理HCT-116细胞，分别导致凋亡增加1.9和2.9倍。而23 μ mol/L DADS对HCT-15细胞的凋亡诱导率仅为1.8倍，对PC-3细胞的凋亡诱导率为1.8倍。因此，DADS诱导的细胞凋亡和NAG-1蛋白表达似乎通过p53发生。
Garlic is appealing as an anti-carcinogenic agent due to its ability to induce apoptosis in vitro and inhibit the formation and growth of tumors in animals in vivo. Diallyl disulfide (DADS) is a constituent of garlic that suppresses neoplastic cell growth and induces apoptosis. We examined the effects of DADS on various cancer cell lines to better understand its effect on apoptosis and apoptosis-related genes. The nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) has proapoptotic and antitumorigenic activities and is upregulated by anticancer agents such as NSAIDs. In this study, human colorectal HCT-116 (wild-type p53), HCT-15 (p53 mutant) and human prostate PC-3 (p53 mutant) cells were exposed to DADS. DADS inhibited cell proliferation in all cell lines albeit to a lesser extent in HCT-15 and PC-3 cells at 11.5 and 23 mumol/L. In HCT-116 cells, DADS induced p53 and NAG-1 in a dose-dependent manner and the induction of p53 preceded that of NAG-1. In HCT-116 cells, NAG-1 protein expression was increased 2.4-fold 0.6 at 4.6 mumol/L and 6.1-fold +/- 1.7 at 23 mumol/L DADS, whereas p53 was induced 1.5-fold +/- 0.1 and 2.3-fold +/- 0.4. DADS did not induce NAG-1 or p53 in p53 mutant cell lines; however, NAG-1 expression was induced by sulindac sulfide. HCT-116 cells treated with 4.6 and 23 mumol/L DADS resulted in a 1.9- and 2.9-fold increase in apoptosis, respectively. In contrast, 23 mumol/L DADS induced apoptosis only 1.8-fold in HCT-15 cells and not at all in PC-3 cells. Thus, DADS-induced apoptosis and NAG-1 protein expression appear to occur via p53.