Bacterial redox protein azurin, tumor suppressor protein p53, and regression of cancer.

Yamada T, Goto M, Punj V, Zaborina O, Chen ML, Kimbara K, Majumdar D, Cunningham E, Das Gupta TK, Chakrabarty AM.

Source

Department of Microbiology, and Surgical Oncology, University of Illinois, 835 South Wolcott Avenue, Chicago, IL 60612, USA.

Abstract

The use of live bacteria in the treatment of cancer has a long and interesting history. We report the use of a purified bacterial redox protein, azurin, that enters human cancer (melanoma UISO-Mel-2) cells and induces apoptosis. The induction of apoptosis occurs readily in melanoma cells harboring a functional tumor suppressor protein p53, but much less efficiently in p53-null mutant melanoma (UISO-Mel-6) cells. A redox-negative mutant form of azurin (M44K/M64E) demonstrates much less cytotoxicity to the UISO-Mel-2 cells than the wild-type protein. Azurin has been shown to be internalized in UISO-Mel-2 cells and is localized predominantly in the cytosol and in the nuclear fraction. In the p53-null UISO-Mel-6 cells, azurin is localized only in the cytosol. Thus, intracellular trafficking of azurin to the nucleus is p53-dependent. Azurin forms a complex with p53, thereby stabilizing it and raising its intracellular level in cytosolic, mitochondrial, and nuclear fractions. Corresponding to an increasing level of p53, an inducer of apoptosis, the level of Bax also increases in mitochondria, allowing significant release of mitochondrial cytochrome c into the cytosol, thus initiating the onset of apoptosis. The M44K/M64E mutant form of azurin, deficient in cytotoxicity, is also deficient in forming a complex with p53 and is less efficient in stabilizing p53 than wild-type azurin. Azurin has been shown to allow regression of human UISO-Mel-2 tumors xenotransplanted in nude mice and may potentially be used in cancer treatment.

PMID:: 12393814; [PubMed - indexed for MEDLINE]
PMCID:: PMC137843

Dat het nieuws over de effectiviteit van een eiwit - Azurin - gehaald uit bacteriën als vaccin in een driejarige studie bij melanomen in muizen goed en veelbelovend is bevestigt nu ook Ralph Moss in zijn nieuwsbrief van 29 november 2002. Het mooie is dat Moss ook een klein historisch overzicht geeft en verwijst naar het Issels behandelcentrum in Mexico. Maar Issels komt oorspronkelijk uit Duitsland en heeft daar een eigne klinierk met een uitstekende reputatie als het gaat om het behandelen van kanker op een meer natuurlijke wijze.

Bron: Nieuwsbrief van Ralph Moss d.d. 29 november 2002:

Protein from Bacteria Shrinks Tumors

Researchers at the University of Illinois at Chicago (UIC) have isolated a protein secreted by bacteria that effectively kills cancer cells. When tested against human melanomas implanted in mice, the protein shrank the tumors, but caused no deaths or adverse reactions
in the laboratory animals. The results of the three-year study were published in
the prestigious Proceedings of the National Academy of Sciences on October 29, 2002.

The bacterial protein that UIC researchers isolated turned out to be a well-known molecule named azurin, which is involved in many everyday processes cells use to generate energy. However, this is the first report that azurin is also effective as an anticancer agent.
Azurin was isolated from the growth medium of Pseudomonas aeruginosa, an antibiotic-resistant "bug" that avoids destruction by killing macrophages, the immune system's first line of defense against foreign invaders.
In the Illinois study, cancerous mice were treated with just half a milligram of azurin per day for 22 days. At the end of the study, the average size of tumors in these mice was 60 percent smaller than in untreated mice. None of the successfully treated animals showed
signs of illness or weight loss. The researchers said that azurin may work by stabilizing a protein called p53, which suppresses tumors by stopping cell division or inducing programmed cell death (apoptosis). Normally, the p53 protein is short-lived. However, azurin binds to the p53 protein and protects it from destruction, thus raising its level within the cell.

Earlier research conducted at Johns Hopkins University using live bacteria to combat cancer had achieved mixed results: though tumors decreased in size, many of the laboratory animals died, presumably because of toxins released by the bacteria or dying cancer cells. This
did not occur in the UIC study. As Dr. Ananda Chakrabarty, distinguished professor of microbiology and immunology at UIC, commented, "Our research suggests we can achieve a therapeutic outcome using bacterial proteins, without the toxicity associated with live bacteria." According to UIC co-investigator Dr. Tapas Das Gupta, preliminary data show that azurin kills several types of cancer cells, including breast and colon cancer. "These results suggest that azurin could be a useful anticancer agent not just for melanoma but for
different kinds of tumors," he said.

It is certainly good to see prominent researchers exploring bacterial treatments for cancer and publishing their results in prestigious journals. However, laboratory studies and animal research are early steps on the long path to the development of treatments that may someday actually benefit cancer patients. History tells us that the chances of this simple and natural treatment being used clinically any time soon are slim.