title: A phthalide derivative isolated from endophytic fungi Pestalotiopsis photiniae induces G1 cell cycle arrest and apoptosis in human HeLa cells.
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 p27(KIP1) protein and p21(CIP1) 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, p21(CIP1), p16(INK4a) 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.
authors.affiliation: College of Life Science, Hebei University, Baoding, China.
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: R L
authors.initials: RL
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001572:Benzofurans / Q000008:administration & dosage* / Q000302:isolation & purification; D018797:Cell Cycle Proteins / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D032462:Cycadopsida; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000187:drug effects; D060026:Endophytes / Q000737:chemistry*; D005434:Flow Cytometry; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D019942:Genes, p16 / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000187:drug effects; D014158:Transcription, Genetic; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000187:drug effects; D013098:Xylariales / Q000737:chemistry*; D000097642:GADD45 Proteins
chemical_list: D051017:Apoptosis Regulatory Proteins; D001572:Benzofurans; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C085126:FOXO1 protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C581727:JunB protein, human; C000606460:TP73 protein, human; C082022:phthalide
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