Affiliation:
1. Hunan Province Key Laboratory of Cancer Cellular and Molecular Pathology, Cancer Research Institute University of South China Hengyang China
2. Department of Oncology, First Affiliated Hospital University of South China Hengyang China
3. Department of Oncology Loudi Central Hospital Loudi China
4. Department of Pathology The First Hospital of Changsha Changsha China
Abstract
AbstractLeukemia is a type of disease in which hematopoietic stem cells proliferate clonally at the genetic level. We discovered previously by high‐resolution mass spectrometry that diallyl disulfide (DADS), which is one of the effective ingredients of garlic, reduces the performance of RhoGDI2 from APL HL‐60 cells. Although RhoGDI2 is oversubscribed in several cancer categories, the effect of RhoGDI2 in HL‐60 cells has remained unexplained. We aimed to investigate the influence of RhoGDI2 on DADS‐induced differentiation of HL‐60 cells to elucidate the association among the effect of inhibition or over‐expression of RhoGDI2 with HL‐60 cell polarization, migration and invasion, which is important for establishing a novel generation of inducers to elicit leukemia cell polarization. Co‐transfection with RhoGDI2‐targeted miRNAs apparently decreases the malignant biological behavior of cells and upregulates cytopenias in DADS‐treated HL‐60 cell lines, which increases CD11b and decreases CD33 and mRNA levels of Rac1, PAK1 and LIMK1. Meanwhile, we generated HL‐60 cell lines with high‐expressing RhoGDI2. The proliferation, migration and invasion capacity of such cells were significantly increased by the treated with DADS, while the reduction capacity of the cells was decreased. There was a reduction in CD11b and an increase in CD33 production, as well as an increase in the mRNA levels of Rac1, PAK1 and LIMK1. It also confirmed that inhibition of RhoGDI2 attenuates the EMT cascade via the Rac1/Pak1/LIMK1 pathway, thereby inhibiting the malignant biological behavior of HL‐60 cells. Thus, we considered that inhibition of RhoGDI2 expression might be a new therapeutic direction for the treatment of human promyelocytic leukemia. The anti‐cancer property of DADS against HL‐60 leukemia cells might be regulated by RhoGDI2 through the Rac1‐Pak1‐LIMK1 pathway, which provides new evidence for DADS as a clinical anti‐cancer medicine.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Hunan Province
Subject
Health, Toxicology and Mutagenesis,Management, Monitoring, Policy and Law,Toxicology,General Medicine
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献