Mechanism of action
MHC-1 (Major Histo-compatibility Class 1 protein)
Tumors can fool the immune system by disguising themselves as normal cells. They can develop a camouflage by expressing high levels of MHC-I in order to to avoid recognition by the specific cells of the immune system that play an important role in antitumor defense – the so called natural killer (NK) cells. Natural killer cells recognize and are blocked by the expression of MHC-I molecules on their target cells. As Avemar reduces the MHC-I level on human tumor cells, it sensitizes them against NK killing, thus reducing their metastatic activities.
ICAM-1 (Intercellular adhesion molecule-1)
In order to defend the body effectively, some cells of the immune system – the leucocytes – require special molecules to help them get through the walls of the vessels and infiltrate the attacker. One of these special molecules is called the ICAM-1. In the presence of abundant amounts of ICAM-1, leukocytes can get through the walls of the vessels easily. It is known that the inner cells of the vessels of some tumors have smaller amount of ICAM-1 compared to normal cells, and this phenomenon can be considered an escape mechanism because efficient leukocyte infiltration is impaired. It has been shown that Avemar makes more ICAM-1 on the cells of the vessels, thus helping the leucocytes to infiltrate the tumor.
RR (ribonucleotid reductase)
Ribonucleotide reductase (RR) is an enzyme, and is needed for DNA synthesis. It was demonstrated that this enzyme is more active in cancer cells, and therefore looks like excellent target for cancer chemotherapy. It was shown that Avemar blocks this enzyme, which favorably impairs the creation of DNA for cancer cells.
PARP is an enzyme that plays a pivotal role in repairing the DNA chains. The activity of this enzyme is extremely high in cancer cells because they are highly dependent upon the active function of their DNA. In the presence of PARP, the cells can correct their eventual mistakes, which coincidentally happen during cell division. Similarly, if PARP does not work well, it leads to DNA fragmentation and thus to cell death (called apoptosis). Avemar inhibits PARP, therefore DNA repair in cancer cells is also impaired. It was also shown that Aveamar does not trigger apoptosis in healthy cells.
COX-1 and COX-2 enzymes
These enzymes play a crucial role in the immune system, and the pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain. Avemar non-selectively inhibits both of these enzymes and this feature may partly explain its anti-inflammatory activities against adjuvant arthritis in rats and rheumatoid arthritis in humans.