Evaluation of the Effects of Serum Starvation and Hypoxic Conditions on Metabolic Pathway Protein Expressions in Breast and Hepatocellular Cancers
Journal Title: Journal of Ankara University Faculty of Medicine - Year 2019, Vol 72, Issue 1
Abstract
Objectives: Adenosine monophosphate (AMP) activating-protein-kinase (AMPK) is a crucial serine/threonine protein kinase that is activated in cellular metabolic stress conditions to maintain cellular energy-homeostasis. Under conditions of stress such as starvation and hypoxia, when the amount of energy in the organism is low or energy consumption is increased, the amount of cellular AMP increases and catabolic reactions such as fatty acid oxidation and glycolysis are induced due to AMPK activation. The most common conditions that cancer cells face in tumormicroenvironment were reported to be nutrient deficiency and lack of oxygen. This study aims to investigate whether cancer cells bear survival advantages with mechanisms of adaptation such as epithelial-mesenchymal-transition and metastasis by the regulation of AMPK under various stress conditions. Materials and Methods: p-AMPK, total-AMPK protein expression levels of breast (SKBR-3, MDA-MB-453) and hepatocellular cancer (HepG2, Huh-7) cell lines under conditions of serum starvation were determined by Western-blot method. In addition, HIF-1α, E-cadherin, p-AMPK and total-AMPK protein expression levels under conditions of hypoxia were also determined by Western-blot method. The effects of stress conditions on regulation of proteins associated with metabolic pathway and invasion in cancer cells were investigated. As a result, the in vitro effects of stress factors which are observed in tumor-microenvironment in vivo were experimentally investigated by this simulation approach. Results: Our findings demonstrate that conditions of starvation and hypoxia may show prominent and statistically significant effects on both cancer cell metabolic regulation and tumor progression. AMPK was shown to be regulated as a result of cellular stress in cancer cells (Huh7, SKBR3) with high AMPK gene expression. Such a regulation seems to provide an adaptive advantage to those cells. Conclusion: Our results will contribute to determining therapeutic strategies targeting cancer cell stress mechanisms and AMPK. In addition, the results will pave the way for future in vivo studies; thus, will contribute to the literature.
Authors and Affiliations
Gürcan Günaydın, Mustafa Emre Gedik
Keywords
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- EP ID EP48688
- DOI 10.4274/atfm.galenos.2019.40316 ARAŞTIRMA MAKALESİ
- Views 248
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