Ling Hui, He Jie, Tan Hui, Yi Lan, Liu Fang, Ji Xiaoxia, Wu Youhua, Hu Haobin, Zeng Xi, Ai Xiaohong, Jiang Hao, Su Qi
Key Laboratory of Tumor Cellular and Molecular Pathology, College of Hunan Province, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, P.R. China.
The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
Int J Oncol. 2017 Feb;50(2):697-707. doi: 10.3892/ijo.2017.3839. Epub 2017 Jan 5.
Diallyl disulfide (DADS) is a primary component of garlic, which has chemopreventive potential. We previously found that moderate doses (15-120 µM) of DADS induced apoptosis and G2/M phase cell cycle arrest. In this study, we observed the effect of low doses (8 µM) of DADS on human leukemia HL-60 cells. We found that DADS could inhibit proliferation, migration and invasion in HL-60 cells, and arrested cells at G0/G1 stage. Then, cell differentiation was displayed by morphologic observation, NBT reduction activity and CD11b evaluation of cytometric flow. It showed that DADS induced differentiation, reduced the ability of NBT and increased CD11b expression. Likewise, DADS inhibited xenograft tumor growth and induced differentiation in vivo. In order to make sure how DADS induced differentiation, we compared the protein expression profile of DADS-treated cells with that of untreated control. Using high resolution mass spectrometry, we identified 18 differentially expressed proteins after treatment with DADS, including four upregulated and 14 downregulated proteins. RT-PCR and western blot assay showed that DJ-1, cofilin 1, RhoGDP dissociation inhibitor 2 (RhoGDI2), Calreticulin (CTR) and PCNA were decreased by DADS. These data suggest that the effects of DADS on leukemia may be due to multiple targets for intervention.
二烯丙基二硫化物（DADS）是大蒜的主要成分，具有化学预防潜力。我们之前发现，中等剂量（15 - 120µM）的DADS可诱导细胞凋亡和G2/M期细胞周期阻滞。在本研究中，我们观察了低剂量（8µM）的DADS对人白血病HL - 60细胞的影响。我们发现DADS可抑制HL - 60细胞的增殖、迁移和侵袭，并使细胞停滞在G0/G1期。然后，通过形态学观察、NBT还原活性和流式细胞术对CD11b进行评估来显示细胞分化。结果表明，DADS诱导分化，降低了NBT还原能力并增加了CD11b表达。同样，DADS在体内抑制异种移植肿瘤生长并诱导分化。为了确定DADS如何诱导分化，我们将DADS处理的细胞与未处理的对照细胞的蛋白质表达谱进行了比较。使用高分辨率质谱，我们鉴定出DADS处理后18种差异表达的蛋白质，包括4种上调和14种下调的蛋白质。RT - PCR和蛋白质印迹分析表明，DADS可使DJ - 1、丝切蛋白1、RhoGDP解离抑制剂2（RhoGDI2）、钙网蛋白（CTR）和增殖细胞核抗原（PCNA）减少。这些数据表明，DADS对白血病的作用可能归因于多个干预靶点。
