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Toxicity study of oxalicumone A, derived from a marine-derived fungus Penicillium oxalicum, in cultured renal epithelial cells.
| Content Provider | Europe PMC |
|---|---|
| Author | Shi, Si Guo, Kunbin Wang, Xiangyu Chen, Hao Min, Jianbin Qi, Shuhua Zhao, Wei Li, Weirong |
| Copyright Year | 2017 |
| Abstract | 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-β-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. |
| ISSN | 17912997 |
| Journal | Molecular Medicine Reports |
| Volume Number | 15 |
| PubMed Central reference number | PMC5428325 |
| Issue Number | 5 |
| PubMed reference number | 28260084 |
| e-ISSN | 17913004 |
| DOI | 10.3892/mmr.2017.6283 |
| Language | English |
| Publisher | D.A. Spandidos |
| Publisher Date | 2017-03-03 |
| Access Restriction | Open |
| Rights License | This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Shi et al. |
| Subject Keyword | Penicillium oxalicum oxalicumone A human kidney-2 cells cytotoxicity apoptosis mitochondria |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Molecular Biology Biochemistry Cancer Research Molecular Medicine Oncology |
