ABSTRACT
OBJECTIVES: To screen the cytotoxic activity of six secondary metabolites isolated from soil fungus Aspergillus niger. Importantly, to investigate the mechanism that pyoluteorin induced human triple-negative breast cancer MDA-MB-231 cells apoptosis in vitro. METHODS: The cell viability assay was tested with CTG assay. Cell cycle, apoptosis and intracellular reactive oxygen species (ROS) production assay were tested with flow cytometry. Additionally, intracellular ROS production assay and mitochondrial membrane potential assay were determined with laser scanning confocal microscopy. The expression of apoptosis-related proteins was determined with Western blot. KEY FINDINGS: Pyoluteorin displayed significantly selective cytotoxicity against human triple-negative breast cancer MDA-MB-231 cells (IC50 = 0.97 µm) with low toxicity against human breast epithelial cell MCF-10A. It was found that pyoluteorin could arrest MDA-MB-231 cells cycle at G2 /M phase and induce cell apoptosis. Further experiments demonstrated that the apoptosis-inducing effect of pyoluteorin was related to reduction of mitochondrial membrane potential, accumulation of ROS and change of apoptosis-related protein expressions. CONCLUSION: Our studies revealed that pyoluteorin had potent proliferation inhibition against MDA-MB-231 cells through arresting cell cycle at G2 /M phase and inducing caspase-3-dependent apoptosis by mitochondrial pathway, implying that pyoluteorin may be a potential lead compound for drug discovery of human triple-negative breast cancer.
Subject(s)
Apoptosis/drug effects , Cell Proliferation/drug effects , G2 Phase Cell Cycle Checkpoints/drug effects , M Phase Cell Cycle Checkpoints/drug effects , Phenols/pharmacology , Pyrroles/pharmacology , Triple Negative Breast Neoplasms/drug therapy , Antineoplastic Agents/pharmacology , Caspase 3/metabolism , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Drug Discovery , Humans , Membrane Potential, Mitochondrial/drug effectsABSTRACT
A new azo compound, penoxalin (1), a new isochroman carboxylic acid, penisochroman B (3), two new natural products, penisochroman A (2) and 2,6-dihydroxy-4-[(2R)-2-hydroxyheptyl] benzoic acid (4), together with four known compounds (5-8) were isolated from wetland soil fungus Penicillium oxalicum GY1. All structures were elucidated by extensive NMR spectroscopic evidences together with mass spectrometry. The absolute configuration of penoxalin (1) was determined by calculated ECD spectrum, while the absolute configuration of new natural product penisochroman A (2) was established for the first time by single crystal X-ray diffraction. In addition, all compounds were evaluated for their cytotoxic activity in vitro. 2, 6-Dihydroxy-4-[(2R)-2-hydroxyheptyl] benzoic acid (4) displayed significant cytotoxicity against human esophageal carcinoma cells OE19 with an IC50 value of 5.50 µM.
Subject(s)
Antineoplastic Agents/isolation & purification , Azo Compounds/isolation & purification , Benzoates/isolation & purification , Penicillium/chemistry , Antineoplastic Agents/chemistry , Azo Compounds/chemistry , Benzoates/chemistry , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , WetlandsABSTRACT
Actinomycetes are outstanding and fascinating sources of potent bioactive compounds, particularly antibiotics. In recent years, rare actinomycetes have had an increasingly important position in the discovery of antibacterial compounds, especially Micromonospora, Actinomadura and Amycolatopsis. Focusing on the period from 2008 to 2018, we herein summarize the structures and bioactivities of secondary metabolites from rare actinomycetes, involving 21 genera.