Diallyl disulfide induces downregulation and inactivation of cofilin�1 differentiation via the Rac1/ROCK1/LIMK1 pathway in leukemia cells

Abstract

Cofilin is associated with cell differentiation; however, to the best of our knowledge, no data have indicated an association between the cofilin 1 pathway and leukemia cell differentiation. The present study investigated the involvement of the cofilin 1 signaling pathway in diallyl disulfide (DADS)-induced differentiation and the inhibitory effects on the proliferation, migration, and invasion of human leukemia HL-60 cells. First, it was identified that 8 µM DADS suppressed cell proliferation, migration and invasion, and induced differentiation based on the reduced nitroblue tetrazolium ability and increased CD11b and CD33 expression. DADS significantly downregulated the expression of cofilin 1 and phosphorylated cofilin 1 in HL-60 leukemia cells. Second, it was verified that silencing cofilin 1 markedly promoted 8 µM DADS-induced differentiation and the inhibitory effect on cell proliferation and invasion. Overexpression of cofilin 1 obviously suppressed 8 µM DADS-induced differentiation and the inhibitory effect on cell proliferation and invasion. Third, the present study examined the mechanisms by which 8 µM DADS decreases cofilin 1 expression and activation. The results revealed that 8 µM DADS inhibited the mRNA and protein expression of Rac1, Rho-associated protein kinase 1 (ROCK1) and LIM domain kinase 1 (LIMK1) as well as the phosphorylation of LIMK1 in HL-60 cells, while 8 µM DADS enhanced the effects of the Rac1-ROCK1-LIMK1 pathway in cells overexpressing cofilin 1 compared with that in control HL-60 cells. These results suggest that the anticancer function of DADS on HL-60 leukemia cells is regulated by the Rac1-ROCK1-LIMK1-cofilin 1 pathway, indicating that DADS could be a promising anti-leukemia therapeutic compound.

LIMK1 promotes peritoneal metastasis of gastric cancer and is a therapeutic target

“…Consistent with on-target inhibition of LIMK1, Dabrafenib decreased p-cofilin levels in a dose-dependent manner, indicating that DAB reduces migration and invasion of GC cells through LIMK1-ADF/cofilin pathway. On the contrary, we found that DADS, another prototypical LIMK1 inhibitor [ 18 , 19 , 32 ], failed to inhibit LIMK1 and cofilin phosphorylation in GC cells. Accordingly, DADS had no inhibitory effect on cell migration and invasion.…”

Nujiangexanthone A Inhibits Hepatocellular Carcinoma Metastasis via Down Regulation of Cofilin 1

“…CFL1 is an important member of the actin depolymerizing factor (ADF) family, which plays an important regulatory role in the depolymerization and polymerization of actin and the remodeling of cytoskeleton ( Gressin et al, 2015 ; Wang et al, 2015 ). Some studies have shown that the activation of CFL1 is closely related to the malignant invasive properties of tumor cells ( Tahtamouni et al, 2013 ; Ling et al, 2020 ; Zhang et al, 2020 ; Wang J. et al, 2021 ). Inhibition of CFL1 activity can reduce the movement and migration of tumor cells, which may be an important target for inhibiting tumor growth and proliferation ( Croise et al, 2014 ).…”

Gastrokine 2 Regulates the Antitumor Effect of JAK2/STAT3 Pathway in Gastric Cancer

“…e role of JAK2/STAT3 pathway in tumors is gradually discovered, and it also has a certain impact on the occurrence and development of gastric cancer [16][17][18]. In this study, we refer to the method in the previous study such as by Ling et al [19]. We first examine the expressions of GKN2 and TFF1 in gastric cancer tissues, adjacent gastric mucosa, and distal gastric mucosa tissues using tissue chip and analyze its role in gastric carcinogenesis.…”