ABSTRACT
Altersolanol A, a fungus-derived tetrahydroanthraquinone, has shown cytotoxic effects on multiple cancer cells. However, its reproductive toxicity in humans has not been well-addressed. The present study was aimed at investigating the cytotoxicity of altersolanol A on human placental trophoblasts including choriocarcinoma cell line JEG-3 and normal trophoblast cell line HTR-8/SVneo in vitro. The results showed that altersolanol A inhibited proliferation and colony formation of human trophoblasts, and the choriocarcinoma cells were more sensitive to the compound than the normal trophoblasts. Altersolanol A induced cell cycle arrest at G2/M phase in JEG-3 cells and S phase in HTR-8/SVneo cells, downregulated the expression of cell cycle-related checkpoint proteins, and upregulated the p21 level. Altersolanol A also promoted apoptosis in human trophoblasts via elevating the Bax/Bcl-2 ratio and decreasing both caspase-3 and caspase-9 levels. Meanwhile, altersolanol A suppressed the mitochondrial membrane potential and induced ROS production and cytochrome c release, which activated the mitochondria-mediated intrinsic apoptosis. Moreover, migration and invasion were inhibited upon altersolanol A exposure with downregulation of matrix metalloproteinase (MMP)-2 in JEG-3 cells and MMP-9 in HTR-8/SVneo cells. Mechanically, altersolanol A supplement decreased the phosphorylation of JNK, ERK, and p38, manifesting the inactivation of MAPK signaling pathway in the human trophoblasts. In conclusion, altersolanol A exhibited potential reproductive cytotoxicity against human trophoblasts via promoting mitochondrial-mediated apoptosis and inhibiting the MAPK signaling pathway.
Subject(s)
Apoptosis , Cell Proliferation , Mitochondria , Trophoblasts , Humans , Trophoblasts/drug effects , Trophoblasts/metabolism , Apoptosis/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Cell Proliferation/drug effects , Membrane Potential, Mitochondrial/drug effects , Female , Reactive Oxygen Species/metabolism , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Line , Pregnancy , Cell Movement/drug effects , Caspase 3/metabolismABSTRACT
Fungal pathogens cause devastating agroeconomic losses. Chemical fungicides are used to control fungal diseases, although this is not an ecofriendly approach. A recent study by Liu et al. highlighted the use of mycoviral gene-incorporating phytopathogenic fungi as biocontrol agents for disease management.
Subject(s)
Fungicides, Industrial , Fungicides, Industrial/pharmacology , Fungi/genetics , Plant Diseases/microbiologyABSTRACT
Tetrahydroanthraquinones are a kind of important microbial secondary metabolites with promising biological activities. Most of them were found in microorganisms, a few were derived from Chinese herbal medicine. In this review, aiming to provide basis for the further research and development of tetrahydroanthraquinone compounds, we summarized the physiological activities of natural tetrahydroanthraquinone compounds, including anti-cancer, anti-microbial, and antidiabetic activities. The source, structure, and action mechanisms of active tetrahydroanthraquinones are described in detail. Furthermore, this review firstly analyzed the structure-activity relationship of tetrahydroanthraquinones. Our study will serve as a valuable guideline for further research on the structural optimization, mechanism study, and development of tetrahydroanthraquinone as novel drugs. Aiming to provide references for further studies and development of tetrahydroanthraquinone compounds.
ABSTRACT
UNLABELLED: The cytotoxic compound Altersolanol A, an anthraquinone derivative was isolated from PM0409092 a fungus of Nyctanthes arbor-tristis (family Oleaceae). It was identified as a Phomopsis sp. by DNA amplification and sequencing of the ITS region. The chemical structure of Altersolanol A was elucidated from its physicochemical properties, 2D NMR spectroscopy and other spectroscopic data. The compound has in vitro cytotoxic activity against 34 human cancer cell lines with mean IC50 (IC70) values of 0.005 µg ml(-1) (0.024 µg ml(-1)) respectively. Altersolanol A, a kinase inhibitor, induces cell death by apoptosis through the cleavage by Caspase-3 and -9 and by decreased anti-apoptotic protein expression. There are several previous reports of the anticancer activity of Altersolanol A, but we report here an extensive study using 36 cell lines which gives wider spectrum of results. SIGNIFICANCE AND IMPACT OF THE STUDY: This study confirms the cytotoxic potential of Altersolanol A isolated from the endophyte Phomopsis sp. (PM0409092) of the plant Nyctanthes arbor-tristis. The compound exhibits in vitro cytotoxicity against 34 human cancer cell lines with mean IC50 (IC70) value of 0.005 µg ml(-1) (0.024 µg ml(-1)). This is an in-depth report of Altersolanol A against a panel of 34 human cancer cell lines and extends observations from previous studies indicating that Altersolanol A can be used for the development of chemotherapeutics. Altersolanol A, a kinase inhibitor, induces cell death by apoptosis through the cleavage of Caspase-3 and -9 and by decreased anti-apoptotic protein expression.