Cancer cells exhibit altered metabolism compared to normal cells. They metabolize glucose to lactate through aerobic glycolysis even when oxygen is present, known as the Warburg effect. Normal cells only undergo glycolysis and produce lactate under low oxygen conditions. Cancer cells also rely on glutaminolysis and have hyperpolarized mitochondria. Inhibiting key steps in glycolysis and mitochondrial metabolism may be potential anti-tumor strategies. Targeting glucose transport, pyruvate oxidation, and mitochondrial metabolism are emerging areas of research.
Use slideshow after downloading for better viewing. The slides cover altered metabolism in cancer with a focus on Warburg effect and drug targeting of metabolic pathways for cancer treatment.
Prepared in Oct 2014
Use slideshow after downloading for better viewing. The slides cover altered metabolism in cancer with a focus on Warburg effect and drug targeting of metabolic pathways for cancer treatment.
Prepared in Oct 2014
Cancer is mainly caused by the conversion of proto-oncogenes into oncogenes. The process is known as oncogenesis.
This slide will help to get an idea about oncogenesis and also the proto-oncogenes which get converted.
Cellular Signaling Pathways have direct implications on our understanding of tumor cell behavior. A general overview is presented here followed by a brief discussion of some of the major pathways currently implicated in cancer progression : Ras/RAF/MAP kinase pathway and PI3K/AKT/mTOR pathway s
p53 has been described as “GUARDIAN ANGEL OF THE GENOME”
because it performs following mechanism:
DNA Repair
Cell growth arrest
Apoptosis (programmed cell death)
P53 is also known as cellular tumour antigen Ag, phosphoprotein
P53 or tumour suppressor p53.
P53 protein is encoded by TP53.
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are mutated or expressed at high levels. Most normal cells undergo a programmed form of rapid cell death (apoptosis) when critical functions are altered.
The epigenetic regulation of DNA-templated processes has been intensely studied over the last 15
years. DNA methylation, histone modification, nucleosome remodeling, and RNA-mediated targeting regulate many biological processes that are fundamental to the genesis of cancer. Here, we
present the basic principles behind these epigenetic pathways and highlight the evidence suggesting that their misregulation can culminate in cancer. This information, along with the promising clinical and preclinical results seen with epigenetic drugs against chromatin regulators, signifies that it
is time to embrace the central role of epigenetics in cancer.
This presentation naming Role of exosomes in cancer help you find exosomal introduction, composition, functions and their role in cancer growth, metastasis, angiogenesis, cancer diagnosis and therapy
A German biochemist, Dr. Otto Warburg showed in 1928 that
tumor cells have a higher rate of glucose metabolism.
▫ He showed that tumor cells convert ten times more glucose
into lactate into glucose (in a given time), under aerobic
conditions.
▫ It is said to be an adaptation of cancer cells, to counter the
variability in energy demand with time. They show high
glycolytic metabolism even with oxygen present.
Carbohydrates are the most abundant biomolecules on the earth. Glycolysis is the first pathway of the cellular respiration used in the breakdown of glucose to extract energy. When energy is needed, metabolic processes mobilize glycogen to produce ATP and give the body fuel. Glycolysis is the major pathway for utilization of glucose & it takes place in the cytoplasm of all the cells of body, as all the glycolytic enzymes required are present in the cytosol. Major pathway for ATP in tissues lacking mitochondria viz. RBC, lens, cornea etc.. Glycolysis is unique because it may be aerobic or anaerobic - meaning it will proceed with or without oxygen also it occurs quickly, and can produce thousands of ATP molecules in milliseconds.
Cancer is mainly caused by the conversion of proto-oncogenes into oncogenes. The process is known as oncogenesis.
This slide will help to get an idea about oncogenesis and also the proto-oncogenes which get converted.
Cellular Signaling Pathways have direct implications on our understanding of tumor cell behavior. A general overview is presented here followed by a brief discussion of some of the major pathways currently implicated in cancer progression : Ras/RAF/MAP kinase pathway and PI3K/AKT/mTOR pathway s
p53 has been described as “GUARDIAN ANGEL OF THE GENOME”
because it performs following mechanism:
DNA Repair
Cell growth arrest
Apoptosis (programmed cell death)
P53 is also known as cellular tumour antigen Ag, phosphoprotein
P53 or tumour suppressor p53.
P53 protein is encoded by TP53.
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are mutated or expressed at high levels. Most normal cells undergo a programmed form of rapid cell death (apoptosis) when critical functions are altered.
The epigenetic regulation of DNA-templated processes has been intensely studied over the last 15
years. DNA methylation, histone modification, nucleosome remodeling, and RNA-mediated targeting regulate many biological processes that are fundamental to the genesis of cancer. Here, we
present the basic principles behind these epigenetic pathways and highlight the evidence suggesting that their misregulation can culminate in cancer. This information, along with the promising clinical and preclinical results seen with epigenetic drugs against chromatin regulators, signifies that it
is time to embrace the central role of epigenetics in cancer.
This presentation naming Role of exosomes in cancer help you find exosomal introduction, composition, functions and their role in cancer growth, metastasis, angiogenesis, cancer diagnosis and therapy
A German biochemist, Dr. Otto Warburg showed in 1928 that
tumor cells have a higher rate of glucose metabolism.
▫ He showed that tumor cells convert ten times more glucose
into lactate into glucose (in a given time), under aerobic
conditions.
▫ It is said to be an adaptation of cancer cells, to counter the
variability in energy demand with time. They show high
glycolytic metabolism even with oxygen present.
Carbohydrates are the most abundant biomolecules on the earth. Glycolysis is the first pathway of the cellular respiration used in the breakdown of glucose to extract energy. When energy is needed, metabolic processes mobilize glycogen to produce ATP and give the body fuel. Glycolysis is the major pathway for utilization of glucose & it takes place in the cytoplasm of all the cells of body, as all the glycolytic enzymes required are present in the cytosol. Major pathway for ATP in tissues lacking mitochondria viz. RBC, lens, cornea etc.. Glycolysis is unique because it may be aerobic or anaerobic - meaning it will proceed with or without oxygen also it occurs quickly, and can produce thousands of ATP molecules in milliseconds.
Ketogenic diet as a treatment of cancer somayeh zaminpira - sorush niknamianbanafsheh61
Cancer disease is the second cause of death in the United States and world-wide. Most Researchers estimate that 595,690
of American people will die from cancer at the end of the year 2017. That means 1,600 deaths/day approximately [1].
Cancer in modern societies is commonly treated with the combination of organ surgery, chemotherapy and radiotherapy.
Many kinds of diet strategies have been experimented. However, none of them have been particularly effective.
Interestingly, there is some applied research suggesting that a very low-carb ketogenic diet may help [2-4]. According to
Otto Warburg hypothesis, the cause of cancer is the change in the metabolism of mitochondrion in human cells. Low
oxygen in tissues in combination with high blood glucose will change the cell respiration from aerobic to anaerobic which
leads to fermentation type of respiration. In this perspective and prospective research, I have shown the very low
carbohydrate ketogenic diet and mostly ketosis, may benefit cancer patients in reducing and weakening cancer cells.
Although further researches are needed, this perspective article could be beneficial in future perspective of alternative
treatments of cancer.
Supplying a huge array of metabolic intermediates for biosynthetic reactions. Normally carbohydrate metabolism supplies more than half of the energy requirements of the body. In fact the brain largely depends upon carbohydrate
Carbohydrate metabolism comprises glycolysis, HMP shunt, Gluconeogenesis, Glycogenolysis, TCA cycle, with Glucose-6-phosphate dehydrogenase deficiency disorder.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Nutritional ketosis condition and specific ketogenic diet, may benefit cancer...banafsheh61
Cancer is the second leading cause of death in the United States. Researchers estimate that 595,690 Americans will die from cancer in 2017. That means approximately 1,600 deaths per day on average.39 Cancer is most commonly treated with a combination of surgery, chemotherapy and radiation. Many different diet strategies have been studied, but none have been particularly effective. Interestingly, there is some applied research suggesting that a very low-carb ketogenic diet may help.40, 41, 42 According to Otto Warburg hypothesis, the cause of cancer is the change in the metabolism of mitochondrion in human cells. Low oxygen in tissues in combination with high blood glucose will change the cell respiration from aerobic to anaerobic which leads to fermentation type of respiration. In this perspective and prospective research, I have shown the very low carbohydrate ketogenic diet and mostly ketosis, may benefit cancer patients in reducing and weakening cancer cells. Although further researches are needed, this perspective article could be beneficial in future perspective of alternative treatments of cancer.
ellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function. Energy is stored in the bonds of glucose (like a stretched rubber band), and when glucose is broken down, much of that energy is released. Some of it is captured in a form that can be used to do work in cells - a molecule called adenosine triphosphate or ATP. The energy that is not captured in ATP is usually given off as heat (one of the things that helps us maintain our normal body temperature).
The process of cellular respiration is similar to a car using gasoline as fuel. As gasoline is the fuel for a car, glucose is the fuel for a cell. A car burns gasoline and uses the energy released for movement. Similarly, a cell ‘burns’ glucose to capture the energy and create ATP. ATP is the primary form of energy that cells use to function.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is also formed during this process. The process can be likened to a waterslide. A person has more energy at the top and loses it as they slide down.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
2. METABOLIC DIFFERENCES BETWEEN
NORMAL AND CANCER CELLS
Normal cells do not metabolize glucose to lactate
when oxygen is available. Only when the oxygen is
absent or limiting do normal cells resort to anaerobic
glycolysis or metabolism of glucose to lactic acid.
cancer cells metabolize glucose to lactate even in the
presence of oxygen (aerobic glycolysis). The idea that
cancer cells exhibit an altered metabolism was given
by Otto Warburg.
4. WARBURG EFFECT
cancer cells under aerobic (well-oxygenated) conditions to metabolize
glucose to lactate (aerobic glycolysis) is known as the Warburg effect .
Warburg made the seminal observation that tumor slices consume glucose
and secrete lactate at a higher rate than normal tissues, even in the presence
of air (aerobic conditions) Normal cells rely on mitochondrial OXPHOS to
produce ATP. Under aerobic conditions, normal cells and tissues metabolize
glucose to carbon dioxide (CO2) and water (H2O) through OXPHOS and
convert glucose to lactate (glycolysis) under hypoxic (poorly oxygenated)
conditions. However, tumor tissues metabolize glucose to lactate even under
aerobic conditions.
Most cancer cells depend on glycolysis, even in the presence of plenty of
oxygen, to generate a considerably lesser amount of ATP with a decreased
use of the OXPHOS mechanism
5. WARBURG EFFECT
Usually, cancer cells
are highly glycolytic
(glucose addiction)
and have a “sweet
tooth” in that they
avidly take up more
glucose than do
normal cells from
outside.
Otto Heinrich Warburg (; 8 October 1883 –
1 August 1970)
In 1931 was awarded the Nobel Prize in
Physiology for his "discovery of the nature
and mode of action of the respiratory
enzyme
6. Pyruvate is the critical
metabolite of the glycolytic
pathway and is responsible
for the formation of lactic
acid catalyzed by lactate
dehydrogenase (LDH) in
cancer cells. Alternatively,
pyruvate can enter into
the Krebs cycle.
GLYCOLYSIS
7. TRICARBOXYLIC ACID CYCLE
Pyruvate generated from the glycolytic
pathway is oxidized by the
enzyme pyruvate dehydrogenase (PDH) to
the acetyl-CoA which combines with
an oxaloacetate molecule to form citric
acid.
Important regulators of the TCA cycle
that are formed from citric acid are alpha-
ketoglutarate formed
from isocitrate, succinate from succinyl-
CoA, fumarate and malonate, and
ultimately oxaloacetate that combines
with acetyl-CoA to keep the TCA cycle
going.
8. GLUTAMINOLYSIS
Cancer cells also take up and metabolize glutamine To
sustain the functioning of the TCA uninterruptedly,
metabolites can be fed into this cycle.
V-Ki-ras2 Kirsten rat sarcoma (KRAS), the viral oncogene
stimulates cancer cell growth through enhanced formation
of alpha-ketoglutarate via the TCA cycle and Increased the
activity of the enzyme, glutamate pyruvate transaminase,
was observed in cancer Thus, glutamine/glutamate
metabolism provides an attractive therapeutic target.
9. ROLE OF MITOCHONDRIA IN CANCER METABOLISM
• Warburg hypothesized that cancer cell mitochondria are
dysfunctional, thus forcing the cells depends upon
exclusively on glycolysis for energy.
• The functional role of mitochondria in tumor cells became
clearer when cancer cells treated with mitochondria-
targeted compounds showed repressed respiration,
decreased cell proliferation, and ATP formation.
• Mitochondrial hyperpolarization is a common feature of
many tumor cell lines.
10. REVERSE WARBURG EFFECT
The glycolytic product, lactic acid, secreted by cancer cells
or fibroblasts is also used by neighboring cancer cells to
make citric acid and sustain cancer progression. The “reverse
Warburg effect” is a new term for “parasitic” cancer metabolism
It was proposed that cancer cells act as metabolic parasites in
that they obtain nutrients from host cells by inducing catabolic
processes. One such process is aerobic glycolysis in host cells.
11. INHIBITING GLYCOLYSIS AS A POTENTIAL ANTI
TUMOR STRATEGY
• Glucose is one of the most abundant sources of energy in cancer
cells.
• During the breakdown of one molecule of glucose in the
presence of oxygen, six molecules of carbon dioxide and water
are released in addition to energy in the form of ATPs. Nearly
34–38 ATP molecules are produced during glycolysis (four
ATPs), the Krebs cycle (two ATPs), and mitochondrial respiration
(34 ATPs).
• If targeting glycolytic and mitochondrial metabolism is a
strategic approach to slow or inhibit the growth of cancer cells.
12. INHIBITING GLUCOSE UPTAKE
• glucose uptake into cancer cells is the rate-limiting step
in glycolysis targeting GLUTs(a family of membrane-bound
proteins called GLUTs) by blocking their glucose transport
channel with small molecules should be a viable mechanism of
nutrient deprivation in tumors.
• Currently, there exist several GLUT inhibitors, including
cytochalasin B and selected tyrosine kinase inhibitors.
• Some of these compounds are relatively less toxic to normal
cells, showing promise in tumor treatment.
13. TARGETING PYRUVATE OXIDATION
• Pyruvate is viewed as a “hub” metabolite (being at the interface
of glycolysis and mitochondrial metabolism) in cell metabolism
and especially plays a central role in regulating
metabolic reprogramming in cancer cells
• Dichloroacetate (DCA), a drug that has shown promising
chemotherapeutic effect in preclinical tumor xenograft studies
and in humans with glioblastoma (an aggressive form of brain
tumor), presumably inhibits PDK, thereby shifting the glucose
metabolism from a glycolytic to oxidative pathway. Thus, DCA
activates PDH by inhibiting PDK, causing increased
mitochondrial metabolism.
14. CONCLUDING REMARKS AND FUTURE PERSPECTIVES
• Several clinical trials for testing DCA as an anticancer agent are ongoing..
• Glycolysis in cancer cells is substantially elevated, antiglycolytic targeting
using 2-DG( 2-deoxyglucose one of the first antiglycolytic antitumor
strategies is the use) as a mono-therapeutic agent in clinical trials has not
been successful. This reflects the metabolic plasticity of cancer cells and their
tendency to escape glucose dependency to other metabolic
pathways through metabolic reprogramming.
• Recent research implicates that mitochondrial metabolism is vital for tumor
growth Targeting mitochondrial metabolism is an emerging area of research
in cancer biology. Cancer cell mitochondrial membrane potential is much
more negative than normal cell mitochondria. Consequently, cationic drugs
can be more selectively targeted to cancer cells.
