Acteoside inhibits human promyelocytic HL-60 leukemia cell proliferation via inducing cell cycle arrest at G0/G1 phase and differentiation into monocyte

Abstract

We investigated the in vitro effects of acteoside on the proliferation, cell cycle regulation and differentiation of HL-60 human promyelocytic leukemia cells. Acteoside inhibited the proliferation of HL-60 cells in a concentration- and time-dependent manner with an IC50, approximately 30 microM. DNA flow cytometric analysis indicated that acteoside blocked cell cycle progression at the G1 phase in HL-60 human promyelocytic leukemia cells. Among the G1 phase cell cycle-related proteins, the levels of cyclin-dependent protein kinase (CDK)2, CDK6, cyclin D1, cyclin D2, cyclin D3 and cyclin E were reduced by acteoside, whereas the steady-state level of CDK4 was unaffected. The protein and mRNA levels of CDK inhibitors (cyclin-dependent kinase inhibitors), such as p21(CIP1/WAF1) and p27(KIP1), were gradually increased after acteoside treatment in a time-dependent manner. In addition, acteoside markedly enhanced the binding of p21(CIP1/WAF1) and p27(KIP1) to CDK4 and CDK6, resulting in the reduction of CDK2, CDK4 and CDK6 activities. Moreover, the hypophosphorylated form of retinoblastoma increased, leading to the enhanced binding of protein retinoblastoma (pRb) and E2F1. Our results further suggest that acteoside is a potent inducer of differentiation of HL-60 cells based on biochemical activities and the expression level of CD14 cell surface antigen. In conclusion, the onset of acteoside-induced G1 arrest of HL-60 cells prior to the differentiation appears to be tightly linked to up-regulation of the p21(CIP1/WAF1) and p27(KIP1) levels and decreases in the CDK2, CDK4 and CDK6 activities. These findings, for the first time, reveal the mechanism underlying the anti-proliferative effect of acteoside on human promyelocytic HL-60 cells.

Secalonic Acid D induced leukemia cell apoptosis and cell cycle arrest of G1 with involvement of GSK-3β/β-catenin/c-Myc pathway

“…[21][22][23] Cyclin D1, CDK4 and E2F1 are important proteins promoting transition of G 1 to S phase. [24][25][26][27] On the other hand, p27 acts as the inhibitor of transition of G 1 to S phase. [28][29][30] In summary, SAD downregulated the expressions of proteins promoting transition of G 1 /S and upregulated the expressions of proteins inhibiting transition of G 1 /S, which was coincident with PI staining and flow cytometry analysis showing increase of G 1 content.…”

Establishment of callus and cell suspension culture of Scrophularia striata Boiss.: an in vitro approach for acteoside production

“…1) is a well-studied PeG that consists of several chemical groups, including caffeic acid, 3,4-dihydroxyphenylethanol, glucose, and rhamnose (Hwang et al 2010). It has been reported that acteoside has extensive biological activities including antioxidant (Chiou et al 2004;He et al 2000), anti-inflammatory (Lee et al 2005(Lee et al , 2006, hepatoprotective (Xiong et al 1999;Zhao et al 2009), cell apoptosis regulation activities (Ohno et al 2002;Xiong et al 1999;Yang and Pu 2006) and cytotoxicity against various tumor cells (Kunvari et al 1999;Lee et al 2007). It may be developed into a promising medication (He et al 2011).…”

Induction of Cyclin D1 Proteasomal Degradation by Branch Extracts from Abeliophyllum distichum Nakai in Human Colorectal Cancer Cells

“…There is a report that four glycosides such as acteoside, isoacteoside, rutin and hisrutrin may be major components of A. distichum (Oh et al, 2003) and acteoside reduced cyclin D1 protein level in human leukemia cell line, HL-60 (Lee et al, 2007). However, it is not clear that the reduction of cyclin D1 protein level by acteoside results from transcriptional regulation or proteasomal degradation.…”