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

Shi,Si; Guo,Kunbin; Wang,Xiangyu; Chen,Hao; Min,Jianbin; Qi,Shuhua; Zhao,Wei; Li,Weirong

doi:10.3892/mmr.2017.6283

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

Authors:
- Si Shi
- Kunbin Guo
- Xiangyu Wang
- Hao Chen
- Jianbin Min
- Shuhua Qi
- Wei Zhao
- Weirong Li
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Affiliations: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China, Key Laboratory of Tropical Marine Bioresources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, Guangdong 510301, P.R. China
Published online on: March 3, 2017 https://doi.org/10.3892/mmr.2017.6283
Pages: 2611-2619
Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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