The ethanol extract from Artemisia princeps Pampanini induces p53-mediated G1 phase arrest in A172 human neuroblastoma cells.
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 G(1) phase arrest in A172 cells. Of the G(1) phase cycle-related proteins examined, the expressions of cyclin-dependent kinase (CDK) 2, CDK4, and CDK6 and of cyclin D(1), D(2), and D(3) 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 G(1)-arrested A172 cells. When these data are taken together, the EAPP was found to potently inhibit the proliferation of human neuroblastoma A172 cells via G(1) phase cell cycle arrest.
Park
Eun Young
EY
Department of Pharmaceutical Biochemistry, College of Pharmacy, Seoul, Republic of Korea.
Lee
Kyung-Won
KW
Lee
Heon-Woo
HW
Cho
Young-Wuk
YW
Baek
Nam-In
NI
Chung
Hae-Gon
HG
Jeong
Tae-Sook
TS
Choi
Myung-Sook
MS
Lee
Kyung-Tae
KT
D019306:Artemisia / Q000737:chemistry*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D004247:DNA / Q000032:analysis; D000431:Ethanol; D016193:G1 Phase / Q000187:drug effects*; D015870:Gene Expression; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology*; D010936:Plant Extracts / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D010936:Plant Extracts; D016159:Tumor Suppressor Protein p53; D000431:Ethanol; D004247:DNA; D018844:Cyclin-Dependent Kinases