Pingyangmycin stimulates apoptosis in human hemangioma-derived endothelial cells through activation of the p53 pathway.
Mol Med Rep
; 10(1): 301-5, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24789513
ABSTRACT
Pingyangmycin (also known as Bleomycin A5) is produced by Streptomyces verticillus var. pingyangensis n.sp., and has antitumor activities against a variety of tumor cells. The aim of the present study was to determine the molecular mechanism(s) underlying the therapeutic effects of pingyangmycin against infantile hemangiomas. Human hemangiomaderived endothelial cells (HemECs) were treated with pingyangmycin at varying concentrations (100, 200 or 300 µg/ml), and the morphological changes and apoptosis levels were assessed. The gene expression changes were determined by cDNA microarray technology. Transmission electron microscopy examination revealed that the pingyangmycintreated HemECs exhibited typical apoptotic characteristics, including chromatin condensation and the formation of apoptotic bodies. AnnexinV staining demonstrated that pingyangmycin caused a significant and dosedependent induction of apoptosis in the HemECs. In the pingyangmycintreated HemECs, 4,752 genes demonstrated at least 2fold expression changes at the mRNA level. Quantitative polymerase chain reaction confirmed that pingyangmycin significantly upregulated the expression of p53, p53induced protein with death domain, Bax, p53 upregulated modulator of apoptosis and p53 inducible gene 3, and downregulated the expression of murine double minute 2. The data demonstrated that the proapoptotic activity of pingyangmycin against infantile hemangiomas involves p53 pathway activation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bleomicina
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Proteína Supressora de Tumor p53
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Apoptose
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Células Endoteliais
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Antibióticos Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2014
Tipo de documento:
Article