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Continuous activation of Nrf2 and its target antioxidant enzymes leads to arsenite-induced malignant transformation of human bronchial epithelial cells.
Abstract Long-term exposure to arsenite leads to human lung cancer, but the underlying mechanisms of carcinogenesis remain obscure. The transcription factor of nuclear factor-erythroid-2 p45-related factor (Nrf2)-mediated antioxidant response represents a critical cellular defense mechanism and protection against various diseases. Paradoxically, emerging data suggest that the constitutive activation of Nrf2 is associated with cancer development, progression and chemotherapy resistance. However, the role of Nrf2 in the occurrence of cancer induced by long-term arsenite exposure remains to be fully understood. By es...
Source: Toxicology and Applied Pharmacology - September 26, 2015 Category: Toxicology Authors: Yang X, Wang D, Ma Y, Xu X, Zhu Z, Wang X, Deng H, Li C, Chen M, Tong J, Yamanaka K, An Y Tags: Toxicol Appl Pharmacol Source Type: research

Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in NSCLC cells.
Abstract Despite excellent initial clinical responses of non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), many patients eventually develop resistance. According to a recent report, vacuolar H+ ATPase (vATPase) is overexpressed and is associated with chemotherapy drug resistance in NSCLC. We investigated the combined effects of EGFR TKIs and vATPase inhibitors and their underlying mechanisms in the regulation of NSCLC cell death. We found that combined treatment with EGFR TKIs (erlotinib, gefitinib, or lapatinib) and vATPase inhibitors (bafilo...
Source: Toxicology and Applied Pharmacology - May 14, 2015 Category: Toxicology Authors: Jin HO, Hong SE, Kim CS, Park JA, Kim JH, Kim JY, Kim B, Chang YH, Hong SI, Hong YJ, Park IC, Lee JK Tags: Toxicol Appl Pharmacol Source Type: research