Scientists have discovered that cells lacking the tumor suppressor Gene PTEN--->a feature of many cancers, including Pca----> are particularly vulnerable to drugs that impair their energy producing mitochondria. Such drugs induce these cancer cells to eat themselves to death in search of food for energy.
Unlike normal cells, cells without PTEN seem driven to preserve their mitochondria, at all costs, says a Team Leader of a research laboratory group. The researchers found that when such cells are treated with certain mitochondria inhibitors, they consume vast quantities of glucose to fuel their efforts. As a result they run out of energy quickly, and die.
Metformin, a widely prescribed drug for diabetes, acts as a mitochondria inhibitor. How efficiently, as to action on the mitochondria has not been well investigated. New findings reported in 'Cell Reports', that drugs like Metformin have the potential to eliminate cancer cells at doses that leave healthy cells intact. The timing of Metformin, Et. Al. is critical. When glucose levels are high, the window of use is lost. Indicating that we may be taking Metformin after meals when glucose levels are high, and it may be beneficial to take these drugs when the glucose levels are low.
Two related compounds, both derived from the root of the same plant, were screened. Both compounds killed cells missing PTEN and another tumor suppressor, p53. Loss of these together is common among men with advanced prostate cancer and is associated with highly metastatic disease. I understand those of us with these losses do not want to hear this, but, it is true. The 2 drugs were found to have little effect on cells having functional PTEN. But the drugs Rotenone and Deguelin, are found to be viable mitochondria inhibitors.
Interesting, experiments found that these drugs would shut down mitochondria in cells with PTEN, as it does with cells without. This is IMPORTANT---> why did cells with PTEN tolerate the toxic compounds, while those without did not?
The answer seems to be how cells use glucose. Researchers found that cells without [PTEN], I.E. Pca cells, use glucose from their environment to generate the energy rich molecule--->ATP, which they import into mitochondria to keep them intact. This is the complete opposite of what mitochondria are suppose to be doing. Mitochondria are suppose to generate ATP for the rest of the cell. For these cells lacking PTEN, unless there is an endless supply of glucose, they quickly use up the sugar and die.
The researchers postulate that eventually, any cell subjected to mitochondria inhibitors will run out of energy and die. Cells without PTEN, just get to die faster. Thus as indicated with Metformin, it would be best to administer these drugs when the blood sugar of the patient is low. As Metformin, and Berberine are indicated to take after meals. This research, may suggest pharmacologists relook the use of Metformin use, especially after what the researchers found with Rotenone and Deguelin.
For the Naturalist here, both drugs are isoflavones, found in the stems vines, and seeds, of the Jicana Root Vegetable, widely grown in Mexico and Central America. In scientific terminology, these compounds block an enzyme [NADH Ubiquinone Reductase], which prevents availability of oxygen for cellular respiration---thus the blocking of the Cells lacking PTEN, from getting Glucose.
Of special note these compounds are not new. They have been used for decades as natural commercial Pesticides, and Insecticides. Its killing action, may be similar to killing cancer cells. No longer approved for its commercial use, due to its poisonous capabilities, yet so are our Chemo Drugs poisons, and when used in correct controlled ways, can kill cancer cells.