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Braz. j. med. biol. res ; 46(8): 643-649, ago. 2013. graf
Article in English | LILACS | ID: lil-684525

ABSTRACT

MP [4-(3′,3′-dimethylallyloxy)-5-methyl-6-methoxyphthalide] was obtained from liquid culture of Pestalotiopsis photiniae isolated from the Chinese Podocarpaceae plant Podocarpus macrophyllus. MP significantly inhibited the proliferation of HeLa tumor cell lines. After treatment with MP, characteristic apoptotic features such as DNA fragmentation and chromatin condensation were observed in DAPI-stained HeLa cells. Flow cytometry showed that MP induced G1 cell cycle arrest and apoptosis in a dose-dependent manner. Western blotting and real-time reverse transcription-polymerase chain reaction were used to investigate protein and mRNA expression. MP caused significant cell cycle arrest by upregulating the cyclin-dependent kinase inhibitor p27KIP1 protein and p21CIP1 mRNA levels in HeLa cells. The expression of p73 protein was increased after treatment with various MP concentrations. mRNA expression of the cell cycle-related genes, p21CIP1 , p16INK4a and Gadd45α, was significantly upregulated and mRNA levels demonstrated significantly increased translation of p73, JunB, FKHR, and Bim. The results indicate that MP may be a potential treatment for cervical cancer.


Subject(s)
Humans , Apoptosis/drug effects , Benzofurans/administration & dosage , Endophytes/chemistry , G1 Phase Cell Cycle Checkpoints/drug effects , Xylariales/chemistry , Apoptosis Regulatory Proteins/genetics , Benzofurans/isolation & purification , Cell Cycle Proteins/drug effects , Cell Proliferation/drug effects , /drug effects , /drug effects , DNA-Binding Proteins/drug effects , Flow Cytometry , Forkhead Transcription Factors/drug effects , Cycadopsida , /drug effects , HeLa Cells , Nuclear Proteins/drug effects , Real-Time Polymerase Chain Reaction , Transcription, Genetic , Transcription Factors/drug effects , Tumor Suppressor Proteins/drug effects
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