HIF-1 (hypoxia-inducible factor-1) regulates the expression of ~100 genes involved in angiogenesis, metastasis, tumor growth, chemoresistance and radioresistance, underscoring the growing interest in targeting HIF-1 for cancer control. In the present study, we investigated the molecular mechanisms underlying brusatol-induced HIF-1α degradation and cell death in colorectal cancer under hypoxia (...

BACKGROUND/AIMS To investigate the roles of hypoxia-inducible factor 1α (HIF-1α), cyclooxygenase-2 (Cox-2) and its product, Prostaglandin E2 (PGE2), in the mechanisms underlying hypoxia-induced survivin expression in human umbilical vein endothelial cells (HUVECs) and to examine the effect of celecoxib, a selective Cox-2 inhibitor, on survivin expression. METHODS HUVECs were exposed to a norm...

Angiogenesis is essential for tumor growth, 1 and it has been shown that anti-angiogenic therapy has been proven to be effective in several cancers such as colorectal cancer 2,3 and hepatocellular carcinoma (HCC). 4 Currently available anti-angiogenic cancer chemotherapy targets the vascular endothelial growth factor (VEGF) pathway by VEGF monoclonal antibody (bevacizumab) 3 or multi-targeted r...

Abstract Background Gliomas are the commonest primary adults’ brain tumors. Hypoxia performs an essential role in gliomas’ initiation as well progression through hypoxia inducible factor (HIF-1α) activation, which could serve a promising target treatment of gliomas. Our study aimed to evaluate types and grades glioma cases detect isocitrate dehydrogenase 1 (IDH1) mutation status expression HIF-...

OBJECTIVE Chronic hypoxia has been recognized as a key regulator in renal tubulointerstitial fibrosis, as seen in diabetic nephropathy, which is associated with the activation of hypoxia-inducible factor (HIF)-1α. We assess here the effects of the biguanide, metformin, on the expression of HIF-1α in diabetic nephropathy using renal proximal tubular cells and type 2 diabetic rats. RESEARCH DES...

Hypoxia-inducible factor-1 (HIF-1) plays a key role in cell adaptation to low oxygen and stabilization of HIF-1 is vital to ensure cell survival under hypoxia. Diabetes has been associated with impairment of the cell response to hypoxia and downregulation of HIF-1 is most likely the event that transduces hyperglycemia into increased cell death in diabetes-associated hypoxia. In this study, we a...

BACKGROUND Ionizing irradiation is a commonly accepted treatment modality for lung cancer patients. However, the clinical outcome is hampered by normal tissue toxicity and tumor hypoxia. Since tumors often have higher levels of active heat shock protein 90 (Hsp90) than normal tissues, targeting of Hsp90 might provide a promising strategy to sensitize tumors towards irradiation. Hsp90 client pro...

Hypoxia-inducible factor 1 alpha (HIF-1α) is closely related with chemoresistance of solid tumors. The purpose of this study was to investigate the ability of noscapine to inhibit HIF-1α and sensitize ovarian cancer cells to cisplatin (DDP) under hypoxic conditions. Herein, we report that noscapine sensitized cobalt-induced chemoresistant ovarian cancer cells to DDP-induced apoptosis and inhibi...

TNF receptor (TNFR)-associated factor TRAF6 is a key activator of NF-κB, playing a critical role in the regulation of innate immune responses and their connection to adaptive immune responses. TRAF6 interactions determine receptor-induced cell death versus survival. TRAF6 has been implicated in cancer but its contributions have not been investigated deeply. In this study, we show that TRAF6 upr...

Hypoxia affects alveolar homeostasis and may induce epithelial injury, which has been implicated in lung diseases such as fibrosis. The underlying cellular and molecular mechanisms are, however, largely unknown. Primary rat alveolar epithelial type II cells (ATII) exposed to graded hypoxia for 24 and 48 h caused a dose-dependent induction of cell cycle arrest and suppression of proliferation, c...