Adaptation Of The Cancer Cell

While Season felt completely broken-down, she knew that she had no choice but to bring her background in nutrition to her own home. To build Kicker’s immunity Season implemented The Ketogenic Diet. The human body produces cancerous cells daily, so building a strong immunity is imperative when fighting off cancer cells and the harsh chemicals from treatment. The Ketogenic Diet is a new cancer treatment, which is free, with virtually no side effects. It can also be conjoined with other cancer treatments. The diet involves cutting carbohydrates, beginning with the worst carbohydrate of all, sugar (Johnson L, 2013). It is a high-fat, adequate-protein, low-carbohydrate diet. The diet forces the body to burn fats rather than carbohydrates. Normally the carbohydrates contained in food are converted into glucose, which are then transported around the body. However, if there are little carbohydrates in the diet then the liver converts fat into fatty acids and ketone bodies. Ketone bodies are water molecules that are produced when the body is consuming very little food, which mimics fasting. Cancer is an obligate glucose metabolizer because it fuels on sugar. One’s normal cells have the metabolic flexibility to adapt from saving glucose by using ketone bodies (Johnson S, 2014). This addressed that because cancer

The anti-apoptotic mutations related to cytochrome c are not the only mechanisms acquired by cells in the development of a tumor. Another important hallmark of cancer is the alteration of cellular metabolism, also known as the Warburg Effect, which demonstrates an increased rate of glycolysis despite the presence of oxygen in tumor cells (Hallmarks). Due to the unlimited and uncontrollable division by tumorigenic cells, the Warburg Effect confers growth advantages compared to non-proliferating cells because it promotes the uptake of glucose, it produces less reactive oxygen species (ROS), and it generates ATP more rapidly than oxidative phosphorylation, all of which are considered to facilitate rapid growth and survival (1).

Background Research: Cellular Respiration is used by the cells to make ATP, by releasing chemical energy from sugars and other carbon based molecules. There are 3 stages to Cellular Respiration, Glycolysis, Krebs Cycle, and the Electron Transport Chain. The inputs of Glycolysis are 2 ATP’s, a Glucose molecule, and a Pyruvate. The inputs for the Krebs Cycle are oxygen, and. In animals, energy is consumed by eating food. In that food they eat, Glucose is found and broken down by the process of cellular respiration, which then converts into energy known as ATP. When there is a lot of ATP and Glucose, the liver converts it into glycogen.

Cancer cells displayed marked alterations in pro-growth signaling pathways and key metabolic pathways relative to non-tumorigenic differentiated cells, often due to loss of tumor suppressor genes and oncogenic driver mutations. The remodeled signaling and metabolic profiles of cancer cells support not only their aberrant proliferation, but also their survival. Further factors such as intra-tumoral heterogeneity, altered redox status, and epigenetic modifications all contribute to the ability of certain tumors to develop drug resistance and persist under standard treatments.

Through many cancer researches in the last decades, it was found that cancer cells often use glucose more voraciously and quite differently from normal cells. Therefore, many researchers and pharmaceutical companies have thought that the nutrient supply and deprivation of the cancer cells will potentially be the next target in disrupting the metabolism of cancer cells.

FDG is a non-physiological analogue of glucose that once injected, is taken up by cell membrane glucose receptors (Mainly, the glucose transporter-1 molecule, GLUT-1) which transport it into the intracellular compartment, where it is phosphorylated into FDG-6-phosphate by the enzymatic action of hexokinase. Cancer cells show increased uptake of glucose (due to an overexpression of glucose transporter proteins) and increased rate of glycolysis. However, following phosphorylation by hexokinase, FDG becomes trapped in the cancer cell, failing to undergo further metabolism due to down-regulation of phosphatase [1] .

Methionine (Met) restriction has become the focus of interest as dietary regimen since the incidence of diseases such as, cardiovascular disorders, diabetes and cancers (Anderson and Weindruch, 2012) are rising at a higher rate, posing health care challenges. Met is the first limiting AA in poultry diet. It has been used to compliment cancer treatment in humans (1) and improve metabolic health (2, 3). However, the liver also plays a vital role in Met metabolism giving that almost half of the daily intake is metabolized there. In addition to its action and as part of the one-carbon metabolic cycle, it can perform critical role in generating S-adenosylmethionine (SAM) which is the major methyl donor for a variety of biologically important reactions.

Chien-Kuang Ding, a current graduate student for MD-PhD degree to become a medical doctor and biomedical researcher in Duke University, Department of Molecular Genetics and Microbiology, Chi laboratory was interviewed on the phone call on November 9, 2016, at 4pm. On the phone called, Ms. Ding explained why her field of work is important in the U.S healthcare system and discussed the requirements for a biomedical scientist to a prospective clinical laboratory scientist in the future. Ms. Ding’s field of work is genomics and metabolism of cancers. She has to understand the basic molecular mechanism of how cancer propagates and react to the environment, such as our immune system, nutrient status, and the therapy. Her field of work is important

II. This section will focus on the influence cancer has on the development, growth, and migration of individual cells.

Cancer glutamine metabolism has been a whole lot complicated to figure it out since there is flexibility of the metabolic systems as well as the number of free nutrients to which the cells have access to simultaneously. The cancer cells in culture are avid consumers of glutamine and metabolize glutamine at higher rates compared to other amino acids. Glucose on the other hand is said to play a crucial role in cancer cell metabolism and glutamine is second and both are needed for proliferating cancer cells for bioenergetics and synthesis of intermediates for macromolecular. The Warbug’s effect states that most cancer cells rely aerobic glycolysis to generate energy for cellular processes which yields less adenosine 5’-triphosphate (ATP). In

This complex converts pyruvate to acetyl CoA, which is necessary for the initiation of the Krebs cycle that ultimately leads to adenosine triphosphate (ATP) production. When thiamin is depleted, the conversion of pyruvate to acetyl CoA is blocked, promoting pyruvate accumulation in the cytosol and eventual lactate production (Gunnerson & Harvey, 2016). The anaerobic pathway of converting pyruvate to lactate is inefficient, producing only 2 moles of ATP compared to the 30 moles of ATP produced during aerobic respiration. Additionally, a lack of ATP following thiamin deficiency shifts energy metabolism to fat stores, which produces ketones for the production of acetyl CoA. However, fat stores are eventually depleted in chronic thiamin deficiency (Dinicolantonio et al.,

AMPK is a heterotrimeric protein, comprised of catalytic α subunits (α1, α2), and β and γ regulatory subunits (β1, β2, γ1, γ2, γ3) (Hardie, 2007)). AMPK is activated by events that either compromise cellular ATP production or increase ATP consumption (Hardie, 2007; Long and Zierath, 2006). The glycogen-binding domain on β subunit also allows AMPK to act as a glycogen sensor (McBride et al., 2009; McBride and Hardie, 2009). AMPK elicits diverse effects on glucose and lipid metabolism, cell cycle, and protein synthesis. Activated AMPK stimulates catabolic pathways that generate ATP through increasing glucose and fatty acid uptake, enhancing glycolysis and fatty acid oxidation, and stimulating mitochondrial biogenesis. Concomitantly, AMPK activation inhibits the rate of anabolic pathways that consume ATP, thus, restores the correct adenylate energy charge (Hardie, 2011). AMPK activation inhibits glycogen and fatty acid synthesis by phosphorylates and inactivates glycogen synthase and Acetyl-CoA carboxylase (ACC), respectively (Hardie, 2007). In addition, AMPK inhibits protein synthesis and cell proliferation (Horman et al., 2002; Motoshima et al., 2006). In conditions where nutrients are limited, AMPK acts as a metabolic checkpoint inhibiting cell growth via suppression of mammalian target of rapamycin complex I (mTORC1) (Gowans et al., 2013).

A regulator of growth and energy metabolism in the pathogenesis and progression of many malignancies

Living organisms need to make energy from food in order to allow rapid cell reproduction and maintain life. Glucose, amino acids, and fatty acids are utilized to generate adenosine triphosphate (ATP), a coenzyme used for an energy carrier. The primary source of carbon and energy for humans and most eukaryotes is glucose [1]. But, since it is polar in nature, glucose cannot diffuse through the plasma membrane’s lipid bilayer. This causes the need for glucose to be transported by a glucose transporter, on the plasma membrane, into the cell. After the uptake of glucose, glycolysis is used to convert the glucose into pyruvate. Glycolysis is a pathway that includes ten enzyme-catalyzed reactions.

Cancer cells are characterized by unlimited cell growth, inefficient apoptosis and excessive anabolism. The process of becoming cancer cells includes gene activation, micro-environmental changes and metabolic reprogramming. All of which compound upon one another and lead the cancer cells to continue with their overwhelming growth and activity. Malignant cancer cells invade and destroy organ infrastructure and replace it with disorganized and damaging cells. (1) The metabolic preference of cancer cells is wide ranging with cervical and glioma cells maintaining a normal oxidative phosphorylation and others exhibiting the switch to glycolysis. (2) This metabolic switch exhibits the adaptation to environmental changes and the tumor’s energy needs and activity. Overall, the carcinogenic process that defines each malignant tumor determines the metabolic profile of the cells. For the purpose of examining the metabolic switch, this paper will focus primarily on the Warburg principle with only slight examination of other cancer cell metabolic profiles.