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.
Highlights
Natural products and their derivatives have been a valuable chemical resource for finding promising drugs for the prevention and treatment of cancer [1]
We found that MP could induce G1 cell cycle arrest and apoptosis in human cervical cancer (HeLa) cells
MP had an antiproliferative effect on HeLa cells
Summary
Natural products and their derivatives have been a valuable chemical resource for finding promising drugs for the prevention and treatment of cancer [1]. Natural products isolated from endophytic fungi have attracted great attention. Some of these endophytes may produce bioactive substances involved in host-endophyte relationships. Many valuable bioactive compounds with anticancer activity have been successfully developed following discovery in endophytic fungi, such as taxol, camptothecin, and phenylpropanoids. A growing body of evidence indicates that the endophytic genus Pestalotiopsis represents a huge and largely untapped resource of natural products with chemical structures that have been optimized by evolution for biological and ecological relevance. MP was first isolated from Alternaria porri and reported to have antifungal activity and cytotoxic activity in cancer cell lines [5,6,7]. The p73 and FKHR pathways may be involved in MP-induced apoptosis and cell cycle arrest. Yang evaluated by flow cytometry using a FacsCalibur (BD Biosciences, USA) instrument and analyzed by the Cell Quest software (BD Biosciences)
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