二烯丙基二硫诱导 HL-60 细胞 G2/M 细胞周期阻滞涉及 Mcl1。

Involvement of Mcl1 in diallyl disulfide-induced G2/M cell cycle arrest in HL-60 cells.

机构信息

Cancer Research Institute, University of South China, Hengyang 421001, Hunan Province, PR China.

出版信息

Oncol Rep. 2012 Jun;27(6):1911-7. doi: 10.3892/or.2012.1704. Epub 2012 Feb 28.

DOI:10.3892/or.2012.1704

Abstract

Diallyl disulfide (DADS) has shown potential as a therapeutic agent in various cancers. Previously, we found that myeloid cell leukemia sequence 1 (Mcl1) was downregulated in DADS-induced cell cycle arrest in HL-60 human leukemia cells. Here, we investigated the role of this protein in DADS-induced G2/M cell cycle arrest in HL-60 cells. We demonstrated that DADS treatment significantly increased the proportion of G2/M phase HL-60 cells (P<0.05) and caused a time-dependent significant downregulation of Mcl1 and the cell cycle-related proteins PCNA and CDK1 (P<0.05). Small interfering RNA-mediated knockdown of Mcl1 expression in HL-60 cells arrested the cell cycle in G2/M phase. By co-immunoprecipitation, we demonstrated that Mcl1 associated with PCNA and CDK1 in G2/M cell cycle arrest in DADS-treated HL-60 cells. DADS decreased the interaction of Mcl1 with PCNA and CDK1, leading to G2/M cell cycle arrest in HL-60 cells. Mcl1 plays an important role in DADS-induced G2/M cell cycle arrest in HL-60 human leukemia cells.

摘要

二烯丙基二硫（DADS）已显示出在各种癌症中作为治疗剂的潜力。之前，我们发现髓样细胞白血病序列 1（Mcl1）在 DADS 诱导的 HL-60 人白血病细胞周期阻滞中下调。在这里，我们研究了该蛋白在 DADS 诱导的 HL-60 细胞 G2/M 细胞周期阻滞中的作用。我们证明 DADS 处理显著增加了 G2/M 期 HL-60 细胞的比例（P<0.05），并导致 Mcl1 以及与细胞周期相关的蛋白 PCNA 和 CDK1 的时间依赖性显著下调（P<0.05）。HL-60 细胞中 Mcl1 的小干扰 RNA 介导的敲低导致细胞周期停滞在 G2/M 期。通过共免疫沉淀，我们证明在 DADS 处理的 HL-60 细胞中，Mcl1 与 PCNA 和 CDK1 相关联，导致 G2/M 细胞周期阻滞。DADS 降低了 Mcl1 与 PCNA 和 CDK1 的相互作用，导致 HL-60 细胞的 G2/M 细胞周期阻滞。Mcl1 在 DADS 诱导的 HL-60 人白血病细胞 G2/M 细胞周期阻滞中起重要作用。