Identification of potential targets for differentiation in human leukemia cells induced by diallyl disulfide.

Abstract

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.

• Authors: Hui Ling, Jie He, Hui Tan, Lan Yi, Fang Liu, Xiaoxia Ji, Youhua Wu, Haobin Hu, Xi Zeng, Xiaohong Ai, Hao Jiang, Qi Su
• Journal: International journal of oncology (Int J Oncol) Vol. 50 Issue 2 Pg. 697-707 (Feb 2017) ISSN: 1791-2423 [Electronic] Greece
• PMID: 28101575 (Publication Type: Journal Article)

Chemical References

• Allyl Compounds
• CD11b Antigen
• Disulfides
• ITGAM protein, human
• Proteome
• diallyl disulfide

Topics

• Allyl Compounds (administration & dosage, pharmacology)
• Animals
• CD11b Antigen (genetics, metabolism)
• Cell Cycle Checkpoints (drug effects)
• Cell Differentiation (drug effects)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Disulfides (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• Gene Expression Regulation, Neoplastic (drug effects)
• HL-60 Cells
• Humans
• Leukemia (drug therapy, genetics, metabolism)
• Mice
• Proteome (drug effects)
• Xenograft Model Antitumor Assays