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Nearly a century later, new findings support Warburg theory of cancer
January 12, 2009German scientist Otto H. Warburg's theory on the origin of cancer earned him the Nobel Prize in 1931, but the biochemical basis for his theory remained elusive.
His theory that cancer starts from irreversible injury to cellular respiration eventually fell out of favor amid research pointing to genomic mutations as the cause of uncontrolled cell growth.
Seventy-eight years after Warburg received science's highest honor, researchers from Boston College and Washington University School of Medicine report new evidence in support of the original Warburg Theory of Cancer.
A descendant of German aristocrats, World War I cavalry officer and pioneering biochemist, Warburg first proposed in 1924 that the prime cause of cancer was injury to a cell caused by impairment to a cell's power plant - or energy metabolism - found in its mitochondria.
In contrast to healthy cells, which generate energy by the oxidative breakdown of a simple acid within the mitochondria, tumors and cancer cells generate energy through the non-oxidative breakdown of glucose, a process called glycolysis. Indeed, glycolysis is the biochemical hallmark of most, if not all, types of cancers. Because of this difference between healthy cells and cancer cells, Warburg argued, cancer should be interpreted as a type of mitochondrial disease.
In the years that followed, Warburg's theory inspired controversy and debate as researchers instead found that genetic mutations within cells caused malignant transformation and uncontrolled cell growth. Many researchers argued Warburg's findings really identified the effects, and not the causes, of cancer since no mitochondrial defects could be found that were consistently associated with malignant transformation in cancers.
Boston College biologists and colleagues at Washington University School of Medicine found new evidence to support Warburg's theory by examining mitochondrial lipids in a diverse group of mouse brain tumors, specifically a complex lipid known as cardiolipin (CL). They reported their findings in the December edition of the Journal of Lipid Research.
Abnormalities in cardiolipin can impair mitochondrial function and energy production. Boston College doctoral student Michael Kiebish and Professors Thomas N. Seyfried and Jeffrey Chuang compared the cardiolipin content in normal mouse brain mitochondria with CL content in several types of brain tumors taken from mice. Bioinformatic models were used to compare the lipid characteristics of the normal and the tumor mitochondria samples. Major abnormalities in cardiolipin content or composition were present in all types of tumors and closely associated with significant reductions in energy-generating activities.
The findings were consistent with the pivotal role of cardiolipin in maintaining the structural integrity of a cell's inner mitochondrial membrane, responsible for energy production. The results suggest that cardiolipin abnormalities "can underlie the irreversible respiratory injury in tumors and link mitochondrial lipid defects to the Warburg theory of cancer," according to the co-authors.
These findings can provide insight into new cancer therapies that could exploit the bioenergetic defects of tumor cells without harming normal body cells.
Boston College
A descendant of German aristocrats, World War I cavalry officer and pioneering biochemist, Warburg first proposed in 1924 that the prime cause of cancer was injury to a cell caused by impairment to a cell's power plant - or energy metabolism - found in its mitochondria.
In contrast to healthy cells, which generate energy by the oxidative breakdown of a simple acid within the mitochondria, tumors and cancer cells generate energy through the non-oxidative breakdown of glucose, a process called glycolysis. Indeed, glycolysis is the biochemical hallmark of most, if not all, types of cancers. Because of this difference between healthy cells and cancer cells, Warburg argued, cancer should be interpreted as a type of mitochondrial disease.
In the years that followed, Warburg's theory inspired controversy and debate as researchers instead found that genetic mutations within cells caused malignant transformation and uncontrolled cell growth. Many researchers argued Warburg's findings really identified the effects, and not the causes, of cancer since no mitochondrial defects could be found that were consistently associated with malignant transformation in cancers.
Boston College biologists and colleagues at Washington University School of Medicine found new evidence to support Warburg's theory by examining mitochondrial lipids in a diverse group of mouse brain tumors, specifically a complex lipid known as cardiolipin (CL). They reported their findings in the December edition of the Journal of Lipid Research.
Abnormalities in cardiolipin can impair mitochondrial function and energy production. Boston College doctoral student Michael Kiebish and Professors Thomas N. Seyfried and Jeffrey Chuang compared the cardiolipin content in normal mouse brain mitochondria with CL content in several types of brain tumors taken from mice. Bioinformatic models were used to compare the lipid characteristics of the normal and the tumor mitochondria samples. Major abnormalities in cardiolipin content or composition were present in all types of tumors and closely associated with significant reductions in energy-generating activities.
The findings were consistent with the pivotal role of cardiolipin in maintaining the structural integrity of a cell's inner mitochondrial membrane, responsible for energy production. The results suggest that cardiolipin abnormalities "can underlie the irreversible respiratory injury in tumors and link mitochondrial lipid defects to the Warburg theory of cancer," according to the co-authors.
These findings can provide insight into new cancer therapies that could exploit the bioenergetic defects of tumor cells without harming normal body cells.
Boston College
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While most of us would never willingly consume a highly endangered species, doing so might be as easy as plucking sushi from a bento box.
Research reveals lipids' unexpected role in triggering death of brain cells
The lipid that accumulates in brain cells of individuals with an inherited enzyme disorder also drives the cell death that is a hallmark of the disease, according to new research led by St. Jude Children's Research Hospital investigators.
Funny, you don't look related
When Charles Darwin visited the Falkland Islands during the voyage of the Beagle in 1835, he saw a wolf-like species, wrote about it in his diaries and correctly commented that it was being hunted in such large numbers that it would soon become extinct.
'Escaped' proteins add to hearing loss in elderly, UF researchers find
Age-related hearing loss is the most common sensory disorder among the elderly. But scientists are still trying to figure out what cellular processes govern or contribute to the loss.
The bizarre lives of bone-eating worms
The females of the recently discovered Osedax marine worms feast on submerged bones via a complex relationship with symbiotic bacteria, and they are turning out to be far more diverse and widespread than scientists expected.
Tags reveal white sharks have neighborhoods in the north Pacific, say Stanford researchers
The white shark may be the ultimate loner of the ocean, cruising thousands of miles in a solitary trek, but a team of researchers has discovered that the sharks have maintained such a consistent pattern of migration that over tens of thousands of years the white sharks in the northeastern Pacific Ocean have separated themselves into a population genetically distinct from sharks elsewhere in the world.
The first men and women from the Canary Islands were Berbers
A team of Spanish and Portuguese researchers has carried out molecular genetic analysis of the Y chromosome (transmitted only by males) of the aboriginal population of the Canary Islands to determine their origin and the extent to which they have survived in the current population.
Promising novel treatment for human cancer -- Chrysanthemum indicum extract
A series of studies have demonstrated that Chrysanthemum indicum possesses antimicrobial, antiinflammatory, immunomodulatory, and neuroprotective effects.
Whale-sized genetic study largest ever for southern hemisphere humpbacks
After 15 years of research in the waters of the South Atlantic and Indian Oceans, scientists from the Wildlife Conservation Society, the American Museum of Natural History, and an international coalition of organizations have unveiled the largest genetic study of humpback whale populations ever conducted in the Southern Hemisphere.
Too much of a good thing? Scientists explain cellular effects of vitamin A overdose and deficiency
If a little vitamin A is good, more must be better, right? Wrong! New research published online in the FASEB Journal shows that vitamin A plays a crucial role in energy production within cells, explaining why too much or too little has a complex negative effect on our bodies.
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