Toxicity study of oxalicumone A, derived from a marine-derived fungus Penicillium oxalicum, in cultured renal epithelial cells

Autor: Weirong Li, Hao Chen, Jianbin Min, Kunbin Guo, Wei Zhao, Si Shi, Shuhua Qi, Xiangyu Wang
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Cancer Research
Cell
human kidney-2 cells
medicine.disease_cause
Kidney
Biochemistry
0302 clinical medicine
Malondialdehyde
Cytotoxicity
bcl-2-Associated X Protein
chemistry.chemical_classification
Membrane Potential
Mitochondrial
Apoptosis Regulator
Caspase 3
apoptosis
Articles
Penicillium oxalicum
Cell biology
mitochondria
medicine.anatomical_structure
Oncology
Proto-Oncogene Proteins c-bcl-2
030220 oncology & carcinogenesis
Molecular Medicine
cytotoxicity
oxalicumone A
endocrine system
Biology
Nitric Oxide
Cell Line
03 medical and health sciences
Acetylglucosaminidase
Genetics
medicine
Humans
fas Receptor
Molecular Biology
Reactive oxygen species
L-Lactate Dehydrogenase
Cell growth
Superoxide Dismutase
Penicillium
Epithelial Cells
Molecular biology
030104 developmental biology
chemistry
Apoptosis
Cell culture
Chromones
Reactive Oxygen Species
Oxidative stress
Zdroj: Molecular Medicine Reports
ISSN: 1791-3004
1791-2997
Popis: Oxalicumone A (POA), a novel dihydrothiophene-condensed chromone, was isolated from the marine-derived fungus Penicillium oxalicum. Previous reports demonstrated that POA exhibits strong activity against human carcinoma cells, thus it has been suggested as a bioactive anticancer agent. To research the toxic effect of POA on cultured normal epithelial human kidney-2 (HK-2) cells and evaluate its clinical safety, cell survival was evaluated by the Cell Counting Kit-8 assay and apoptosis was evaluated by Hoechst 33258 staining, flow cytometry, caspase-3 activity assay and western blotting. 2',7'-Dichlorofluorescin diacetate and JC-1 dye staining was used to evaluate reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP), respectively. The results indicated that POA inhibited HK-2 cell growth and promoted apoptosis, by increasing levels of Fas cell surface cell receptor and the B-cell lymphoma 2 associated protein X apoptosis regulator (Bax)/B-cell lymphoma 2 apoptosis regulator (Bcl-2) ratio. POA treatment also induced release of ROS and loss of MMP in HK-2 cells. Compared with untreated control, a significant decrease was also demonstrated in superoxide dismutase activity and glutathione content with POA treatment, accompanied by enhanced release of N-acetyl-beta-D-glucosaminidase, increased leakage of lactate dehydrogenase, increased malondialdehyde formation and increased release of nitric oxide. In conclusion, the present in vitro study revealed that POA exhibits antiproliferation activity on HK-2 cells, through stimulation of apoptosis and oxidative stress injury, which may be relevant to its clinical application. The present study may, therefore, offer valuable new information regarding the use of POA as a candidate novel antitumor drug for clinical use.
Databáze: OpenAIRE
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