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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2009-11-30
pubmed:abstractText
Oroxylin A, a naturally occurring monoflavonoid extracted from Scutellariae radix, exhibits anticancer activity and induces apoptosis in human hepatocellular carcinoma HepG2 cells according to our previous data. In this study, we investigate whether p53 is involved in oroxylin A-triggered viability inhibition and apoptosis induction in cancer cells. In a panel of different cancer cell lines, more potent inhibitory effects of oroxylin A were observed in wtp53 cells than those in mtp53 or p53-null cells. Moreover, p53-siRNA-transfected HepG2 cells showed lower levels of apoptosis induced by oroxylin A than control-siRNA-transfected cells. Likewise, after oroxylin A treatment, p53-null K-562 cells displayed promoted apoptosis rate when transfected with wtp53 plasmid. Western blot and real-time RT-PCR assay revealed that oroxylin A markedly upregulated p53 protein expression in HepG2 and p53-overexpressing K-562 cells, but had no influence on p53 mRNA synthesis. Furthermore, after co-treatment with cycloheximide, oroxylin A still exerted a little effect on p53 expression. The negative regulator of p53, MDM2 protein was detected, and downregulated expression was observed. In the presence of MG132, an inhibitor of proteasome-mediated proteolysis, no change in p53 expression was obtained. Additionally, the antioxidant N-acetyl-L-cysteine could obviously abrogate p53 stabilization triggered by oroxylin A. Therefore, it is summarized that oroxylin A stabilized p53 expression and induced apoptosis at the posttranslational level via downregulating MDM2 expression and interfering MDM2-modulated proteasome-related p53 degradation. This indicated that oroxylin A could be served as a potential, novel agent candidate for cancer therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/5,7-dihydroxy-6-methoxy-2-phenylchro..., http://linkedlifedata.com/resource/pubmed/chemical/Acetylcysteine, http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants, http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids, http://linkedlifedata.com/resource/pubmed/chemical/MDM2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/NAD(P)H Dehydrogenase (Quinone), http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-mdm2, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1098-2744
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1159-69
pubmed:dateRevised
2011-2-4
pubmed:meshHeading
pubmed-meshheading:19626645-Acetylcysteine, pubmed-meshheading:19626645-Antineoplastic Agents, pubmed-meshheading:19626645-Antioxidants, pubmed-meshheading:19626645-Apoptosis, pubmed-meshheading:19626645-Blotting, Western, pubmed-meshheading:19626645-Cells, Cultured, pubmed-meshheading:19626645-Endothelium, Vascular, pubmed-meshheading:19626645-Flavonoids, pubmed-meshheading:19626645-Humans, pubmed-meshheading:19626645-NAD(P)H Dehydrogenase (Quinone), pubmed-meshheading:19626645-Neoplasms, pubmed-meshheading:19626645-Proto-Oncogene Proteins c-mdm2, pubmed-meshheading:19626645-RNA, Messenger, pubmed-meshheading:19626645-RNA, Small Interfering, pubmed-meshheading:19626645-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19626645-Scutellaria baicalensis, pubmed-meshheading:19626645-Tumor Suppressor Protein p53, pubmed-meshheading:19626645-Umbilical Veins
pubmed:year
2009
pubmed:articleTitle
Involvement of p53 in oroxylin A-induced apoptosis in cancer cells.
pubmed:affiliation
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't