Researchers discover gene that permanently stops cancer cell proliferation

Researchers at Case Western Reserve University School of Medicine have discovered a mutant form of the gene, Chk1, that when expressed in cancer cells, permanently stopped their proliferation and caused cell death without the addition of any chemotherapeutic drugs. This study illustrates an unprecedented finding, that artificially activating Chk1 alone is sufficient to kill cancer cells.

"We have identified a new direction for cancer therapy and the new direction is leading us to a reduction in toxicity in cancer therapy, compared with chemotherapy or radiation therapy," said Dr. Zhang, assistant professor, Department of Pharmacology at the School of Medicine, and member of the university's Case Comprehensive Cancer Center. "With this discovery, scientists could stop the proliferation of cancer cells, allowing physicians time to fix cells and genetic errors." While studying the basic mechanisms for genome integrity, Dr. Zhang's team unexpectedly discovered an active mutant form of human Chk1, which is also a non-natural form of this gene. This mutation changed the protein conformation of Chk1 from the inactive form into an active form. Remarkably, the research team discovered that when expressed in cancer cells, this active mutant form of Chk1 permanently stopped cancer cell proliferation and caused cell death in petri dishes even without the addition of any chemotherapeutic drugs. The biggest advantage of this potential strategy is that no toxic chemotherapeutic drug is needed to achieve the same cancer killing effect used with a combination of Chk1 inhibitors and chemotherapeutic drugs. Cells respond to DNA damage by activating networks of signaling pathways, termed cell cycle checkpoints. Central to these genome pathways is the protein kinase, called Chk1. Chk1 facilitates cell survival, including cancer cells, under stressful conditions, such as those induced by chemotherapeutic agents, by placing a temporary stop on the cell cycle progression and coordinating repair programs to fix the DNA errors. It has long been suggested that combining Chk1 inhibition with chemotherapy or radiotherapy should significantly enhance the anticancer effect of these therapies. This idea has serves as the basis for multiple pharmaceutical companies searching for potential Chk1 inhibitors that can effectively combine with chemotherapy in cancer therapy. To date, no Chk1 inhibitor has passed the clinical trial stage III . This led Dr. Zhang's team to look for alternative strategies for targeting Chk1 in cancer therapy. Future research by Dr. Zhang and his team will consider two possible approaches to artificially activating Chk1 in cancer cells. One possibility is to use the gene therapy concept to deliver the active mutant form of Chk1 that the team discovered, into cancer cells. The other is to search for small molecules that can induce the same conformational change of Chk1, so that they can be delivered into cancer cells to activate Chk1 molecules. The consequence of either would be permanent cell proliferation inhibition and cancer.

The only way I can even pretend to follow this is to think of the workings of a very large and complicated computer system.. it does sound interesting. When I was in high school the technology was a knife to cut up a frog. The biochemistry(?) sounds fascinating.

this active mutant form of Chk1 permanently stopped cancer cell proliferation and caused cell death in petri dishes even without the addition of any chemotherapeutic drugs.

Another link says This New Drug Appears to Cause Cancer Cells to Self-Destruct

"Cancer cells have very different metabolic processes than normal cells, in terms of how they derive their energy . . .

"There are two major pathways your cells use to covert sugar into energy: glucose oxidation and glycolysis:

"Glucose oxidation is the primary energy metabolism in normal cells and takes place in your mitochondria, which are the little "power plants" inside your cell; it requires the presence of oxygen, as its name suggests. This is why you breathe and your heart beats to circulate oxygen throughout your body. Glucose oxidation is sometimes referred to as cellular respiration.

"Glycolysis takes place in your cell's cytoplasm (The protoplasm outside the nucleus of a cell). It can occur without the presence of oxygen. Glycolysis is less efficient for normal cells, but it is a cancer cell's preferred means of energy metabolism, and it depends on the availability of sugar.

"So, when your cells are oxygen-starved they have a backup plan. They can extract energy from sugar without the presence of oxygen, by glycolysis.

"Pyruvate is required for glucose oxidation. There is an enzyme (pyruvate dehydrogenase kinase, or PDK) that acts as gatekeeper to regulate the flow of pyruvate into the mitochondria. If PDK is active, it suppresses the transport of pyruvate into the mitochondria, and your cell is forced to rely on glycolysis, even if oxygen is available.

"If PDK is inactive, pyruvate is shuttled into the mitochondria, even if oxygen is low.

"Unlike normal cells, cancer cells are masterful at deriving energy from glycolysis—they have very active PDK. The way to make a cancer cell unhappy is by suppressing PDK, forcing the cell to use glucose oxidation, instead of glycolysis. This is called the Warburg theory of cancer, or the Warburg hypothesis5. This is where DCA comes in. . .

"DCA suppresses PDK (the mitochondrial gatekeeper), and this fires up the cell's mitochondria. Not only does this force the cancer cell to abandon its preferred metabolic process, but it flips the cell's 'suicide switch' as well. This happens because mitochondria are the primary regulators of apoptosis, or cellular suicide—they are loaded with sensors that react to abnormalities by pushing the cell's self-destruct button.

"When a cancer cell's mitochondria realize it's a cancer cell, it spontaneously kills itself. This is the reason chemotherapy and radiation result in such terrible side effects—your healthy cells actually die much more easily because of this self-destruct button.

"The reason cancer is so fast growing is that the mitochondria have been deactivated, so the cells evade apoptosis [cellular suicide], as well as being able to grow in the absence of oxygen (glycolysis). DCA reverses this. In effect, DCA directly causes cancer cell apoptosis and works synergistically other cancer therapies, such as radiation, gene therapy, and viral therapy. A number of scientific studies have been performed to date, and most are encouraging."

There are unwelcomed side effects to all this..

"A Safer Alternative: FOODS that Cause Cancer Cells to Self-Destruct

"What if there were natural agents that induced cancer cell suicide, without the side effects of DCA? As it turns out, these agents DO exist—and you may already have some in your kitchen pantry or supplement cabinet. Here are a few21:

"Co-Q10/Ubiquinol
"Curcumin (the active agent in the spice turmeric)
"Capsaicin (the compound that makes hot peppers hot)
"Se-methylselenocysteine aka methylselenocysteine (found in garlic and broccoli)
"Ellagic acid (from pomegranates and other fruits)

"There are many all-natural cancer-prevention strategies, and research shows they may cut your risk in half. Consequently, by implementing multiple strategies, you can radically lower your risk of cancer as well as other chronic diseases. . . ."

And of course all this just happened to evolve just right . . . .

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