Ursolic acid sensitizes radioresistant NSCLC cells expressing HIF-1α through reducing endogenous GSH and inhibiting HIF-1α
| Autor: | Qiyi Yi, Bing Song, Wensen Jin, Xinrong Qi, Gang Wang, Maohu Yu, Linlin Xiao, Qian Zhang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Cell ursolic acid Biology 03 medical and health sciences 0302 clinical medicine Radioresistance medicine hypoxia inducible factor-1α MTT assay Viability assay Radiosensitivity glutathione non-small cell lung cancer Articles Transfection Molecular biology 030104 developmental biology medicine.anatomical_structure Oncology Apoptosis Cell culture 030220 oncology & carcinogenesis Cancer research radiosensitization |
| Zdroj: | Oncology Letters |
| ISSN: | 1792-1082 1792-1074 |
| DOI: | 10.3892/ol.2016.5468 |
| Popis: | In previous studies, the present authors demonstrated that effective sensitization of ionizing radiation-induced death of tumor cells, including non-small cell lung cancer (NSCLC) cells, could be produced by oleanolic acid (OA), a pentacyclic triterpenoid present in plants. In the present study, it was investigated whether ursolic acid (UA), an isomer of OA, had also the capacity of sensitizing radioresistant NSCLC cells. The radioresistant cell line H1299/M-hypoxia inducible factor-1α (HIF-1α) was established by transfection with a recombinant plasmid expressing mutant HIF-1α (M-HIF-1α). Compared with parental H1299 cells and H1299 cells transfected with empty plasmid, H1299/M-HIF-1α cells had lower radiosensitivity. Following the use of UA to treat NSCLC cells, elevation of the radiosensitivity of cells was observed by MTT assay. The irradiated H1299/M-HIF-1α cells were more sensitive to UA pretreatment than the irradiated cells with empty plasmid and control. The alteration of DNA damage in the irradiated cells was further measured using micronucleus (MN) assay. The combination of UA treatment with radiation could induce the increase of cellular MN frequencies, in agreement with the change in the tendency observed in the cell viability assay. It was further shown that the endogenous glutathione (GSH) contents were markedly attenuated in the differently irradiated NSCLC cells with UA (80 µmol/l) pretreatment through glutathione reductase/5,5'-dithiobis-(2-nitrob-enzoic acid) (DTNB) recycling assay. The results revealed that UA treatment alone could effectively decrease the GSH content in H1299/M-HIF-1α cells. In addition, the inhibition of HIF-1α expression in radioresistant cells was confirmed by western blotting. It was then concluded that UA could upregulate the radiosensitivity of NSCLC cells, and in particular reduce the refractory response of cells expressing HIF-1α to ionizing radiation. The primary mechanism is associated with reduction of endogenous GSH and inhibition of high expression of intracellular HIF-1α. UA should therefore be deeply studied as a potential radiosensitizing reagent for NSCLC radiotherapy. |
| Databáze: | OpenAIRE |
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