This essay is reposted from http://www.grouppekurosawa.com
One of the most important anti-cancer/leukemia targets is the genetic factor NF-kappaB. In the last few years, it has become apparent that NF-kappaB is a critical factor for the continued survival of cancer stem cells. These stem cells are the ONLY cells that can promote the continued proliferation of cancer and leukemia cells.
As previously discussed, cancer and leukemia cells will die on their own if cancer stem cells are eliminated from the bulk of malignant cells. The average cancer/leukemia cell can propagate on its own for unknown generations, but eventually it will die. These cells, contrary to previous dogma, are NOT immortal. Cancer stem cells, on the other hand, are immortal. As long as they exist, the respective cancer or leukemia will not be eliminated from the body.
Three years ago a study was conducted showing that parthenolide, the active ingredient in feverfew, killed acute myeloid leukemia and chronic myeloid leukemia blast cell progenitor and stem cells. The target was NF-kappaB.
Unfortunately, parthenolide is insoluble in water and therefore poorly bioavailable. A synthetic form of parthenolide was developed that has 70% oral bioavailability. This compound induces the rapid death of primary stem cells from myeloid and lymphoid cell populations and is toxic to the bulk tumor load. Again, the target is NF-kappaB.
The following study, published in May of this year, did an extensive analysis of the cancer stem cells found in prostate cancers. They found that these cancer specific stem cells were pro-inflammatory. The four main pathways activated were JAK/STAT signaling, cell adhension and extracellular matrix interactions, focal adhesion signaling and WNT signaling. I will be discussing WNT signaling in the next essay. If parthenolide blocks the activation of NF-kappaB in these stem cells, the cells die of apoptosis. Normal stem cells are not affected.
Other studies have found that cancer stem cells do not contain an excessive amount of NF-kappaB. However, in cancer stem cells the NF-kappaB is chronically activated.
The following new study is very exciting in its implications. First, it shows that NF-kappaB inhibitors such as parthenolide preferentially inhibit breast cancer stem cells. Second, it compares and contrasts parthenolide with the chemo drug paclitaxel (Taxol) with respect to their efficacy against cancer stem cells and normal cancer cells.
At a low dose of 1 microM, parthenolide inhibits the growth of cancer stem cells by 40%, and normal cancer cells by 3%. When the dose is increased to 5 microM, parthenolide inhibited stem cell growth by 95% and normal cancer cell growth by 66%.
Paclitaxel, on the other hand, at a dose of 2.5 nanoM inhibited normal cancer cell growth by 50% and stem cell growth by 40%.
The authors found that a combination of parthenolide and paclitaxel acted synergistically to reduce tumor mass in cancer bearing mice.
We have two ways to reduce NF-kappaB in cancer cells. Glutamine is the first and parthenolide is the second. Parthenolide, due to its poor bioavailability, must be administered topically in a 70% DMSO gel. I have 99% pure parthenolide if anyone wants it. It cost $100 for 10 grams payable via PayPal. The PayPal payment address is firstname.lastname@example.org. The 10 grams is mixed in four ounces of the DMSO gel, a standard commercial size. Parthenolide is effective in low concentrations so a little could go a long way.
In the next essay, I will discuss the WNT pathway that stimulates the growth of cancer stem cells. Cyclic AMP inhibitors, of which there are many, inhibit this pathway.