The Ethanol Extract from Artemisia princeps Pampanini Induces p53-Mediated G 1 Phase Arrest in A172 Human Neuroblastoma Cells

Abstract

In the present study, the antiproliferative effects of the ethanol extract of Artemisia princeps Pampanini (EAPP) and the mechanism involved were investigated. Of the various cancer cells examined, human neuroblastoma A172 cells were most sensitive to EAPP, and their proliferation was dose- and time-dependently inhibited by EAPP. DNA flow cytometry analysis indicated that EAPP notably induced the G₁ phase arrest in A172 cells. Of the G₁ phase cycle-related proteins examined, the expressions of cyclin-dependent kinase (CDK) 2, CDK4, and CDK6 and of cyclin D₁, D₂, and D₃ were found to be markedly reduced by EAPP, whereas cyclin E was unaffected. Moreover, the protein and mRNA levels of the CDK inhibitors p16^INK4a, p21^CIP1/WAF1, and p27^KIP1 were increased, and the activities of CDK2, CDK4, and CDK6 were reduced. Furthermore, the expressions of E2F-1 and of phosphorylated pRb were also decreased, and the protein levels of p53 and pp53 (Ser15) were increased. Up-regulation of p21^CIP1/WAF1 was found to be mediated by a p53-dependent pathway in EAPP-induced G₁-arrested A172 cells. When these data are taken together, the EAPP was found to potently inhibit the proliferation of human neuroblastoma A172 cells via G₁ phase cell cycle arrest.