 |
|
Small molecule offers big hope against cancer
January 17, 2007DCA is an odourless, colourless, inexpensive, relatively non-toxic, small molecule. And researchers at the University of Alberta believe it may soon be used as an effective treatment for many forms of cancer.
Dr. Evangelos Michelakis, a professor at the U of A Department of Medicine, has shown that dichloroacetate (DCA) causes regression in several cancers, including lung, breast, and brain tumors.
Michelakis and his colleagues, including post-doctoral fellow Dr. Sebastian Bonnet, have published the results of their research in the journal Cancer Cell.
Scientists and doctors have used DCA for decades to treat children with inborn errors of metabolism due to mitochondrial diseases. Mitochondria, the energy producing units in cells, have been connected with cancer since the 1930s, when researchers first noticed that these organelles dysfunction when cancer is present.
Until recently, researchers believed that cancer-affected mitochondria are permanently damaged and that this damage is the result, not the cause, of the cancer. But Michelakis questioned this belief and began testing DCA, which activates a critical mitochondrial enzyme, as a way to "revive" cancer-affected mitochondria.
The results astounded him.
Michelakis and his colleagues found that DCA normalized the mitochondrial function in many cancers, showing that their function was actively suppressed by the cancer but was not permanently damaged by it.
More importantly, they found that the normalization of mitochondrial function resulted in a significant decrease in tumor growth both in test tubes and in animal models. Also, they noted that DCA, unlike most currently used chemotherapies, did not have any effects on normal, non-cancerous tissues.
"I think DCA can be selective for cancer because it attacks a fundamental process in cancer development that is unique to cancer cells," Michelakis said. "Cancer cells actively suppress their mitochondria, which alters their metabolism, and this appears to offer cancer cells a significant advantage in growth compared to normal cells, as well as protection from many standard chemotherapies. Because mitochondria regulate cell death—or apoptosis—cancer cells can thus achieve resistance to apoptosis, and this appears to be reversed by DCA."
"One of the really exciting things about this compound is that it might be able to treat many different forms of cancer, because all forms of cancer suppress mitochondrial function; in fact, this is why most cancers can be detected by tests like PET (positron emission tomography), which detects the unique metabolic profile of cancer compared to normal cells," added Michelakis, the Canada Research Chair in Pulmonary Hypertension.
Another encouraging thing about DCA is that, being so small, it is easily absorbed in the body, and, after oral intake, it can reach areas in the body that other drugs cannot, making it possible to treat brain cancers, for example.
Also, because DCA has been used in both healthy people and sick patients with mitochondrial diseases, researchers already know that it is a relatively non-toxic molecule that can be immediately tested in patients with cancer.
Furthermore, the DCA compound is not patented and not owned by any pharmaceutical company, and, therefore, would likely be an inexpensive drug to administer, Michelakis added.
However, as DCA is not patented, Michelakis is concerned that it may be difficult to find funding from private investors to test DCA in clinical trials. He is grateful for the support he has already received from publicly funded agencies, such as the Canadian Institutes for Health Research (CIHR), and he is hopeful such support will continue and allow him to conduct clinical trials of DCA on cancer patients.
"This preliminary research is encouraging and offers hope to thousands of Canadians and all those around the world who are afflicted by cancer, as it accelerates our understanding of and action around targeted cancer treatments," said Dr. Philip Branton, Scientic Director of the CIHR Institute of Cancer.
University of Alberta
Scientists and doctors have used DCA for decades to treat children with inborn errors of metabolism due to mitochondrial diseases. Mitochondria, the energy producing units in cells, have been connected with cancer since the 1930s, when researchers first noticed that these organelles dysfunction when cancer is present.
Until recently, researchers believed that cancer-affected mitochondria are permanently damaged and that this damage is the result, not the cause, of the cancer. But Michelakis questioned this belief and began testing DCA, which activates a critical mitochondrial enzyme, as a way to "revive" cancer-affected mitochondria.
The results astounded him.
Michelakis and his colleagues found that DCA normalized the mitochondrial function in many cancers, showing that their function was actively suppressed by the cancer but was not permanently damaged by it.
More importantly, they found that the normalization of mitochondrial function resulted in a significant decrease in tumor growth both in test tubes and in animal models. Also, they noted that DCA, unlike most currently used chemotherapies, did not have any effects on normal, non-cancerous tissues.
"I think DCA can be selective for cancer because it attacks a fundamental process in cancer development that is unique to cancer cells," Michelakis said. "Cancer cells actively suppress their mitochondria, which alters their metabolism, and this appears to offer cancer cells a significant advantage in growth compared to normal cells, as well as protection from many standard chemotherapies. Because mitochondria regulate cell death—or apoptosis—cancer cells can thus achieve resistance to apoptosis, and this appears to be reversed by DCA."
"One of the really exciting things about this compound is that it might be able to treat many different forms of cancer, because all forms of cancer suppress mitochondrial function; in fact, this is why most cancers can be detected by tests like PET (positron emission tomography), which detects the unique metabolic profile of cancer compared to normal cells," added Michelakis, the Canada Research Chair in Pulmonary Hypertension.
Another encouraging thing about DCA is that, being so small, it is easily absorbed in the body, and, after oral intake, it can reach areas in the body that other drugs cannot, making it possible to treat brain cancers, for example.
Also, because DCA has been used in both healthy people and sick patients with mitochondrial diseases, researchers already know that it is a relatively non-toxic molecule that can be immediately tested in patients with cancer.
Furthermore, the DCA compound is not patented and not owned by any pharmaceutical company, and, therefore, would likely be an inexpensive drug to administer, Michelakis added.
However, as DCA is not patented, Michelakis is concerned that it may be difficult to find funding from private investors to test DCA in clinical trials. He is grateful for the support he has already received from publicly funded agencies, such as the Canadian Institutes for Health Research (CIHR), and he is hopeful such support will continue and allow him to conduct clinical trials of DCA on cancer patients.
"This preliminary research is encouraging and offers hope to thousands of Canadians and all those around the world who are afflicted by cancer, as it accelerates our understanding of and action around targeted cancer treatments," said Dr. Philip Branton, Scientic Director of the CIHR Institute of Cancer.
University of Alberta
Mitochondrial Current Events and Mitochondrial News RSSMini heart attacks lessen damage from major ones
Researchers have discovered one potential mechanism by which briefly cutting off, then restoring, blood flow to arteries prior to a heart attack lessens the damage caused, according to a study published today in the journal Cardiovascular Research.
New research helps explain genetics of Parkinson's disease
A new study by Narendra et al. suggests that Parkin, the product of the Parkinson's disease-related gene Park2, prompts neuronal survival by clearing the cell of its damaged mitochondria.
DNA provides 'smoking gun' in the case of the missing songbirds
It sounds like a tale straight from "CSI": The bully invades a home and does away with the victim, then is ultimately found out with the help of DNA evidence.
Revealing the evolutionary history of threatened sea turtles
It's confirmed: Even though flatback turtles dine on fish, shrimp, and mollusks, they are closely related to primarily herbivorous green sea turtles.
Embryonic heart exhibits impressive regenerative capacity
A new study demonstrates that the embryonic mouse heart has an astounding capacity to regenerate, a phenomenon previously observed only in non-mammalian species.
A link between mitochondria and tumor formation in stem cells
Researchers report on a previously unknown relationship between stem cell potency and the metabolic rate of their mitochondria -a cell's energy makers. Stem cells with more active mitochondria also have a greater capacity to differentiate and are more likely to form tumors.
Making metabolism more inefficient can reduce obesity
In a discovery that counters prevailing thought, a study in mice has found that inactivating a pair of key genes involved in "fat-burning" can actually increase energy expenditure and help lower diet-induced obesity. These unusual findings, appearing this week in the JBC, might lead to some new roads in weight-loss therapy.
Researchers discover that growing up too fast may mean dying young in honey bees
Reactive oxygen species (ROS) occur as a by-product of aerobic metabolism and impair cellular function by damaging proteins, nucleotides and lipids.
Extinct may not be forever for some species of Galapagos tortoises
Yale scientists report that genetic traces of extinct species of Galapagos tortoises exist in descendants now living in the wild, a finding that could spur breeding programs to restore the species, The report appears in Proceedings of the National Academy of Sciences.
Cutting calories could limit muscle wasting in later years
Chemical concoctions can smooth over wrinkles and hide those pesky grays, but what about the signs of aging that aren't so easy to fix, such as losing muscle mass? Cutting calories early could help, say University of Florida researchers who studied the phenomenon in rats.
More Mitochondrial Current Events and Mitochondrial News Articles
 | Drug-Induced Mitochondrial Dysfunction This is the definitive, one-stop resource on preclinical drug evaluation for potential mitochondrial toxicity, addressing the issue upfront in the drug development process. It discusses mitochondrial impairment to organs, skeletal muscle, and nervous systems and details methodologies used to assess mitochondria function. It covers both in vitro and in vivo methods for analysis and includes the... |
 | Mitochondrial Medicine: Mitochondrial Metabolism, Diseases, Diagnosis and Therapy Mitochondrial Medicine is a relatively new area where several disciplines from basic science to clinical medicine converge. Mitochondrial medicine deals with diseases that are related to mitochondrial dysfunction due to a number of causes from free radical damage to genetic mutation. A primary feature of mitochondrial dysfunction is impaired cellular bioenergetics. This book is based upon... |
 | Mitochondrial Medicine by Salvatore DiMauro, Michio Hirano, Eric A. Schon Mitochondrial dysfunction is increasingly being recognized as the basis of a wide variety of human diseases. Providing an authoritative update on our current knowledge of mitochondrial medicine, this text draws together world authorities from various fields to present general therapeutic strategies, as well as the treatments presently available in different specialties - thus making it essential... |
 | Human Mitochondrial DNA and the Evolution of Homo sapiens (Nucleic Acids and Molecular Biology) Mitochondrial DNA is one of the most explored genetic systems because of what it can tell us about the human past. This volume takes a unique perspective, presenting the disparate strands that must be tied together to exploit this system. From molecular biology to anthropology, statistics to ancient DNA, this first volume of three presents the global picture of human mitochondrial DNA variation.... |
| Neurodegenerative Diseases: Mitochondrial Dysfunction and Oxidation Damage (Neuroscience Intelligence Unit Series) | |
 | Mitochondrial Function and Biogenesis (Topics in Current Genetics) Mitochondria are complex organelles, possessing a double-membrane and even their own genome, the mtDNA. They play a pivotal role in cellular metabolism, respiration, and production of ATP essential for the normal function of all human organ systems. It is not surprising, therefore, that genetic defects of mitochondrial functions cause a wide spectrum of human diseases. This book provides the... |
 | Mitochondrial Pharmacology and Toxicology 2006 by Antonio J. M. Moreno This book examines recent developments in mitochondrial medicine, pharmacology and... |
| Mitochondrial Pathogenesis: From Genes and Apoptosis to Aging and Disease (Annals of the New York Academy of Sciences) The identification of the mitochondrion represents a tremendous achievement in the attempt by scientists to understand the essence of life and life's energy. We now know that the mitochondrion is the intracellular powerhouse that generates ATP, the chemical energy source, through a chain of reactions called oxidative phosphorylation. The realm of mitochondrial research has steadily broadened, and... | |
| Anion Carriers of Mitochondrial Membranes by A. Azzi, K. A. Nalecz, M. J. Nalecz | |
| Thirty Years of Progress in Mitochondrial Bioenergetics and Molecular Biology: Proceedings of the 23rd Bari Meeting on Bioenergetics, Interanational Symposium ... and molecul (Progress in Cell Research) by International Symposium on Thirty Years of Progress in Mitochondrial b The topics contained in this book represent timely and currently exciting areas of research focused on mitochondria. It forms a comprehensive and up-to-date record of present knowledge at the molecular level of many important mitochondrial processes. Major achievements as well as new openings in the field have been stressed in many of the contributions to the book. Thus, it represents a valuable... |
| © 2008 BrightSurf.com |