oxalylglycine and Colorectal-Neoplasms

Sestrin2 (SESN2) is an antioxidant protein that modulates cellular redox homeostasis through regeneration of peroxiredoxins. It has beneficial effects in oxidative or metabolic stress conditions as an upstream regulator of AMP-activated protein kinase (AMPK). Since hypoxia causes oxidative and metabolic stress, this study investigated the effect of SESN2 on signaling pathways altered by hypoxia in colon cancer cells. SESN2 overexpression in HEK293 cells inhibited hypoxia-inducible factor-1α (HIF-1α), which plays a crucial role in tumor growth and development in hypoxia. Moreover, infection with adenovirus-SESN2 (Ad-SESN2) decreased hypoxia or CoCl

Topics: Adenoviridae; Amino Acids, Dicarboxylic; AMP-Activated Protein Kinases; Animals; Cell Hypoxia; Cell Movement; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; Genetic Vectors; HCT116 Cells; HEK293 Cells; HT29 Cells; Humans; Hydroxylation; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Nuclear Proteins; Prolyl Hydroxylases; Response Elements; Signal Transduction; Ubiquitination

Hypoxia-inducible factor 1 (HIF-1) is a hypoxia-induced transcription factor that regulates gene expression in critical pathways involved in tumour growth and metastasis. Metallothionein (MT) is a group of small molecular weight cysteine-rich proteins with a broad variety of functions. The present study aimed to analyse the prognostic impact of HIF-1alpha and MT expression in colorectal cancer and to evaluate a possible link of combined HIF-1alpha and MT expression with colorectal cancer progression.. We investigated the relationship of HIF-1alpha and MT with each other and clinicopathological parameters including proliferative activity (Ki67) and apoptosis (terminal desoxyribonucleotide transferase-mediated dUTP nick-end labelling) using immunohistochemistry.. HIF-1alpha expression was identified as an independent prognostic parameter in multivariate survival analysis and characterised an aggressive cancer phenotype. In addition, HIF-1alpha was significantly linked to an increased expression of MT.. HIF-1alpha expression qualified as an independent prognostic and characterised an aggressive cancer phenotype associated with an increased expression of MT. Our study suggests that MT can be added to the complex biological pathways induced by hypoxia in human cancer tissue.

Topics: Amino Acids, Dicarboxylic; Apoptosis; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Epithelial Cells; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Kaplan-Meier Estimate; Male; Metallothionein; Phenotype; Reactive Oxygen Species; Staining and Labeling