High glucose promotes prostate cancer cells apoptosis via Nrf2/ARE signaling pathway

J.-Y. Chen, F.-B. Wang, H. Xu, L.-F. Xu, D. Chen, W.-H. Liu, X. Mu, Y.-Q. Wen

Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China. chenjunyidoctor@163.com

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• Geriatrics

OBJECTIVE: To explore the influences of high glucose on the proliferation and apoptosis of prostate cancer cells and analyze its possible mechanism of action.

MATERIALS AND METHODS: Human prostate cancer cell line LNCaP was divided into control group, mannitol group, and high glucose group. Then, the proliferation in each group was detected via methyl-thiazolyl-tetrazolium (MTT) assay. Hoechst staining assay was performed to determine the apoptosis level in each group. Western blotting was employed to measure the expression levels of apoptosis-related proteins and nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and γ-glutamylcysteine synthetase (γ-GCS) proteins. The cellular reactive oxygen species (ROS) level was measured through 2,7-dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. Enzyme-linked immunosorbent assay (ELISA) was carried out to detect the content of lactate dehydrogenase (LDH) and inflammatory factors.

RESULTS: High glucose significantly promoted the proliferation of prostate cancer cells LNCaP (p<0.01) and increased the apoptosis level of cells (p<0.01). In high glucose group, the expression level of Caspase-3 protein was overtly increased (p<0.01), while that of B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein (Bax) was significantly decreased (p<0.01). High glucose group had clearly increased the content of ROS (p<0.01), LDH (p<0.01), and interleukin-6 (IL-6) (p<0.01), but decreased the content of IL-10 (p<0.01). High glucose notably lowered the protein expression levels of Nrf2, HO-1, and γ-GCS in the cells (p<0.01).

CONCLUSIONS: High glucose represses the activation of the Nrf2/anti-oxidation response element (ARE) signaling pathway in prostate cancer cells and increases the content of ROS, IL-6, and the expression of apoptotic proteins in the cells, thus promoting the apoptosis of prostate cancer cells.

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