Pingyangmycin stimulates apoptosis in human hemangioma-derived endothelial cells through activation of the p53 pathway.
Pingyangmycin (also known as Bleomycin A5) is produced by Streptomyces verticillus var. pingyangensis n.sp., and has anti‑tumor 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 hemangioma‑derived 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 pingyangmycin‑treated HemECs exhibited typical apoptotic characteristics, including chromatin condensation and the formation of apoptotic bodies. Annexin‑V staining demonstrated that pingyangmycin caused a significant and dose‑dependent induction of apoptosis in the HemECs. In the pingyangmycin‑treated HemECs, 4,752 genes demonstrated at least 2‑fold expression changes at the mRNA level. Quantitative polymerase chain reaction confirmed that pingyangmycin significantly upregulated the expression of p53, p53‑induced 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 pro‑apoptotic activity of pingyangmycin against infantile hemangiomas involves p53 pathway activation.
Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Jun-Bo
JB
Tu
Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Quan-Yan
QY
Li
Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Fei
F
Jiang
Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Xiao-Yi
XY
Hu
Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Rui-Zhao
RZ
Ma
Department of Oral and Maxillofacial Surgery, Weihai Stomatological Hospital, Weihai, Shandong 264200, P.R. China.
Qiang
Q
Dong
Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Hao
H
Zhang
Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Parukjan
P
Pattar
Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Shi-Xian
SX
Li
D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000633:toxicity; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006391:Hemangioma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D001761:Bleomycin; C025703:bleomycetin; D051736:Proto-Oncogene Proteins c-mdm2