30.04.2014
“Metabolism of Cancer Cells”
by: Asst. Prof. Dr. Peela Jagannadha Rao
Department of Biochemistry, Faculty of Medicine
Quest International University Perak (QIUP)
DATE: 30 April 2014
TIME: 4 – 5 p.m
VENUE: Lecture Room 4 (Level 3), Applied Sciences Building, QIUP
ABSTRACT
The link between cancer and altered metabolism is not new, as studies from the early period of cancer biology research indicated that metabolic changes were a common feature of cancerous tissues. Much of the on-going work in the field has focused on rapidly proliferating in vitro tumor models and cells. Future clinical data describing the metabolic profiles of human tumors will be required to determine which metabolic alterations are most prevalent in specific tumor types. However, despite the lack of comprehensive clinical data, there has been substantial recent progress in understanding the molecular events that regulate some of these metabolic phenotypes. Multiple molecular mechanisms, both intrinsic and extrinsic, converge to alter core cellular metabolism and provide support for the basic needs of dividing cells i.e., rapid ATP generation to maintain energy status, increased synthesis of macro-molecules and tightened maintenance of cellular redox status. Metabolic changes are a common feature of cancerous tissues. The best characterized metabolic phenotype observed in tumor cells is the Warburg effect, which is a shift of ATP generation from oxidative phosphorylation to ATP generation from glycolysis, even under normal oxygen concentrations. This effect is regulated by the PI3K, hypoxia-inducible factor (HIF), p53, MYC and AMP-activated protein kinase (AMPK)–liver kinase B1 (LKB1) pathways. But metabolic adaptation in tumor cells extends beyond the Warburg effect. It is going to be clear that alterations to metabolism, balance the need of the cell for energy with its important need for macro-molecular building blocks and maintenance of proper redox balance. To this end, a key molecule produced as a result of altered cancer metabolism is reduced nicotinamide adenine dinucleotide phosphate (NADPH), which functions as a co-factor and provides reducing power in many enzymatic reactions that are crucial for macro-molecular biosynthesis and it is also an antioxidant and forms part of the defense against reactive oxygen species (ROS) that are produced during rapid proliferation. High levels of ROS can cause damage to macro-molecules, which can induce senescence and apoptosis. Cells counteract the detrimental effects of ROS by producing antioxidant molecules, such as reduced glutathione (GSH) and thioredoxin (TRX). Several of these antioxidant systems, including GSH and TRX, depend on the reducing power of NADPH to maintain their activities. Finally, genetic changes can alter tumor cell metabolism. The micro-environment around tumors such as hypoxia, pH and low glucose concentrations have a major role in determining the metabolic phenotype of tumor cells. Thus mutations in oncogenes and tumor suppressor genes leads to alterations in multiple intracellular signaling pathways that affect tumor cell metabolism and re-engineer it to effect abnormal survival and enhanced proliferation and growth.
