Why Methyl Jasmonate is a Stand Alone Treatment for Cancer and Leukemia

There is increasing evidence that methyl jasmonate, a plant stress hormone, may be the ultimate stand alone treatment for ALL cancers and leukemias. The original research on MJ as a treatment for cancer began in Israel, but now scientists in other countries, including the US and Japan, have begun their own research programs on the anti-cancer properties of this simple compound.

MJ is a simple compound that in crude form is used to prevent the infection of plants by bacteria. In pure form, it is used by cosmetics companies as a scent. Now we know that MJ is a viable treatment for cancer and different forms of leukemia. Eventually, the Israeli scientists who discovered the anti-cancer properties of MJ will receive the Nobel Prize.

The ultimate anti-cancer compound is toxic to cancer but not normal cells. Preferably there would be no side effects such as vomiting and hair loss. Also, it would be nice if this compound was relatively inexpensive and easy to administer. Naturally, this is all wishful thinking. No such compound exists.

Or does it?

We all know that damage to the outer mitochondrial membrane is a primary signal for programmed cell death. However, the initiation of apoptosis AKA programmed cell is a complicated process. It requires the activation of many genes and the inactivation of others. Genetic defects in key gene activity can block the initiation of apoptosis. For example, during periods of oxidative stress or DNA damage the universal tumor suppressor p53 is activated. This protein promotes programmed cell death, thereby inhibiting the development of cancers. Unfortunately, over 50% of all cancers harbor genetic defects in the p53 gene rendering it ineffective in promoting cancer cell death.

Methyl jasmonate selectively kills cancer cells by binding to their mitochondria membranes and inducing damage. This damage initiates apoptosis, BUT it bypasses the normal complicated biochemical steps involved classical programmed cell death. MJ induced cell death is direct. It does not depend on the activation of other genes or the p53 status of the cancer cell.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15753398&itool=pubmed_docsum

We now know why MJ is so effective in killing cancer and leukemia cells.

First, a small technical review is in order.

It is well established that cancer cells are capable of using aerobic glycolysis to promote their growth and survival. The average cancer cell uses a combination of both glycolysis and respiration in its metabolism. The high aerobic glycolysis metabolism is critically important for cancer cells because it produces a rapid source of ATP. In addition, the glycolytic pathway activates the pentose monophosphate shunt. This shunt provides compounds that regenerate glutathione, the major anti-oxidant in cells, while producing precursors for the biosynthesis of nucleic acid, phospholipids, fatty acids, cholesterol, and porphyrins. Clearly high levels of aerobic glycolysis are absolutely necessary for the growth and survival of cancer and leukemia cells.

Over the last few years it has become clear that the enzyme hexokinase 2 (HK2), the first step in the metabolism of glucose, is over expressed in cancer cells. This enzyme, in order to be active, MUST bind the outer membrane of the mitochondria. Recent reports have found that the docking protein for HK2 on the mitochondrial membrane is VDAC, voltage dependent anion channel. The presence of VDAC on the mitochondrial membrane, the overexpression of the HK2 enzyme and the binding of HK2 to VDAC are fundamental aspects of the Warburg Effect, the aerobic glycolytic metabolism of cancer cells.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=17879147&itool=pubmed_docsum

VDAC is a very interesting protein. It is the most prevalent protein in the mitochondrial outer membrane. This pore protein transports ADP and inorganic phosphate into the mitochondria for the production of ATP, the energy source of all cells. It also transports ATP out of the mitochondria into the cytoplasm of the cell. If VDAC activity is inhibited, apoptosis occurs.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=17135295&itool=pubmed_docsum

In order for HK2 to promote aerobic glycolysis, it is dependent on the VDAC mediated transport of ATP to the bound HK2 enzyme.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=18704666&itool=pubmed_docsum

HK2 binds VDAC after it is phosphorylated by enzymes such as AKT. AKT is a known cell growth and survival factor for cancer cells.

The binding of HK2 to VDAC apparently stabilizes VDAC and prevents its inactivity. As long as VDAC remains active, apoptosis is prevented.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15574336&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=14701745&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=18039843&itool=pubmed_docsum

A number of VDAC inhibitors are now known to induce apoptosis. But this is only part of the story.

The release of cytochrome C, normally bound to the inner mitochondrial membrane, initiates the complex biochemical pathways associated with apoptosis. When HK2 is dislodged from the VDAC complex, cytochrome C is released into the cytoplasm. However, this effect is probably indirect. The inner mitochondrial membrane contains a protein called the permeability transition pore (PTP). Disruption of the functioning of this pore causes depolarization, membrane swelling, and the release of cytochrome C from its membrane binding site.

Hexokinase 2 detachment from the VDAC complex promotes the inactivation of both the VDAC and PTP pore complexes. This results in an inhibition of ATP synthesis and the promotion of cell death by necrosis, apoptosis and autophagy.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=18350175&itool=pubmed_docsum

VDAC is not simply a binding site for HK2. The binding of HK2 to VDAC stabilizes the pore complex and prevents apoptosis.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=18308720&itool=pubmed_docsum

A few months ago a study was published showing that methyl jasmonate binds directly to hexokinase and detaches it from VDAC. This results in an inactivation of VDAC and glycolysis, while promoting mitochondrial membrane swelling, and the release of cytochrome C into the cytoplasm. Cellular death rapidly follows.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=18469866&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=18408762&itool=pubmed_docsum

In addition to promoting apoptosis, methyl jasmonate also promotes necrosis. MJ promoted necrosis occurs in at least two different ways. First, it damages the mitochondria and promotes ATP depletion. Second, it promotes the expression of the tumor necrosis factor receptor in the membrane of cancer cells. TNF is the single most potent anti-cancer immune hormone yet identified.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=18690087&itool=pubmed_docsum

Methyl jasmonate is administered in two different ways.

As an aerosol MJ is added to distilled water in a small personal steamer such as that manufactured by Vicks. It is sold by Amazon.com and large drug stores. 2 grams (2 milliliters) of MJ is added to the surface of the water where it will float as a light oil. The steamer is turned to high and the steam/MJ is inhaled into the lung. Breathe through the mask for 15-20 minutes. This is done every six days. I see no reason why it could not be done more often.

Posted in: Cancer, Leukemia, Methyl Jasmonate, Tumors