  |
|
|
|
The use of bacteria in the treatment of cancer began with the work of the surgeon, Dr. Coley. In 1888, Dr. Coley observed that a bone cancer patient in his final stages suffered two skin infections with Streptococcus and yet fully recovered. Recognizing that administration of live bacteria was dangerous, Coley prepared a mixture of toxins from two species of bacteria that seemed to work as well as live cultures. He worked with Parke-Davis to commercialize the product, but the pharmaceutical company modified the product, reducing its effectiveness. Although commercial production of the product ended in 1953, interest in the product remains high.
Bacterial enterotoxins Diarrhea is commonly caused by infectious strains of the bacterium Escherichia coli, and is much more common in peoples of under-developed countries. Interestingly, these people have a much lower incidence of colon cancer. Pitari and co-workers 3 studied the enterotoxins secreted by the E. coli during infections to see if they could find a basis for its apparent protective effect. When the workers added the enterotoxin to colon cancer cells grown in tissue culture, they found that the bacterium evolved a strategy of molecular mimicry in order to infect its host. The enterotoxin peptides (protein fragments) are structurally similar to the endogenous (found in the body) peptides, guanylin and uroguanylin. The endogenous peptides are involved with fluid and electrolyte balances in the intestines, but the enterotoxins cause the excessive secretions of diarrhea. Both classes of peptides stimulate a cascade of biochemical reactions culminating in the influx of calcium into the cell, and inhibition of DNA synthesis. Apparently, the calcium influx provides a protective effect against colon cancer, by some unknown manner. In colon cancer cells, the guanylin peptides are not produced, resulting in a loss of tumor suppression. These findings could provide a novel means of treating colon cancer. In order to restore functioning of the tumor suppressor pathway, the physician could administer the endogenous peptides, a modified form of the bacterial toxin, or a component of the pathway itself, including calcium. Bacterial proteins Yamada and co-workers 4 at the University of Illinois purified a protein called azurin from the bacterium Pseudomonas aeruginosa. Laboratory mice received a commercial strain of melanoma cancer cells, and tumors were allowed to establish and grow. The mice then received or not the azurin preparation. After 22 days, the azurin treated group showed a significant reduction in tumor size, compared to the controls. The studies indicated that azurin acts by binding to and stabilizing the tumor suppressor protein, p53. The longer acting p53 is found in all parts of the cell, and induces apoptosis, or cell death. The study illustrated the potential of low molecular bacterial proteins as anticancer agents.
The copyright of the article Bacterial toxins for the treatment of cancer in Cancer Treatment is owned by David Olle. Permission to republish Bacterial toxins for the treatment of cancer in print or online must be granted by the author in writing.
|
|
|
|
