The malaria parasite enters the red blood cells and sequesters iron. The mechanism of action of artemisinin in "zapping" the malaria parasite is through the affinity of artemisinin to iron. The artemisinin compound contains two oxygen atoms hooked together in what is termed an endoperoxide linkage. In the presence of free iron this linkage breaks down, forming very reactive free radicals that cause rapid and extensive damage and death to the parasite.
From Malaria Parasite to Cancer Cells
Dr. Henry Lai, Ph.D., bioengineering research professor at the University of Washington has focused much of his research years working with electromagnetic fields and their effects on biological tissue. One area of his research has been in using electromagnetic fields to treat diseases, such as destroying the malaria parasite through pulsing magnetic fields.
During a phone conversation in 1994, Dr. Lai asked a colleague who had just returned from a malaria seminar what was new in the field. His colleague told him, "Well, there is a new antimalarial called artemisinin. Come over to my office and I'll give you a paper on it." Dr. Lai went over to his office, took the paper, and started reading it on his way back to his own office. Suddenly, the idea of using artemisinin to selectively kill cancer cells "jumped into his mind", as he says. Dr. Lai had made the simple but profound connection to the known fact that all cancer cells sequester iron just as the malaria parasite does.
In order to sequester iron needed for their rapid cell division, cancer cells also have higher percentages of receptors that transport iron (called transferrin receptors) into the cells.
Dr. Lai was aware of the high concentration of transferrin receptors in cancer cells because, at that same time, he was doing research trying to attach small minute magnetic beads to transferrin receptors on cancer cells. They could then be shaken with an oscillating magnetic field. The idea was that with enough shaking, the cancer cell would break apart. He called this the 'shake and break'. With this method, he found he could only kill about 1/3 of the cells in 8 hours.
Breast cancer cells have five to fifteen times as many of these iron-receptors as normal breast cells, and an elevated level of iron is a common finding in breast cancer tissue as well as in other cancer cells. Leukemia cells have the highest concentration of iron, up to 1000 times more iron than normal cells.
Dr. Lai wondered if artemisinin compounds would demonstrate the same free radical damaging cascade in cancer cells as they do to the malaria parasite. Starting in 1994 and later with research funding from the Breast Cancer Fund in San Francisco, Dr. Lai and his colleague, Dr. Narendra Singh, Ph.D., M.D., initiated some test tube studies with cancer cells. Meanwhile, the University of Washington patented his potential cancer treatment.
Test Tube Results with Artemisinin
The breast cancer cell research resulted in a 28% reduction of breast cancer cells treated only with artemisinin, and a staggering 98% decrease in breast cancer cells that were treated with artemisinin and an iron-enhancing molecule, transferrin, within 16 hours. These same treatments had no significant effect on normal human breast cells. This research pointed to the involvement of free iron in the toxic effect of artemisinin toward cancer cells, while basically sparing healthy cells. ("Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells," Life Sciences 70 {2001) 49-56)
These results become even more potentially important because the breast cancer cells used in the study were radiation resistant, a difficult situation to overcome.
An earlier study with human leukemia cells demonstrated 100% cancer cell destruction in half the time (8 hours) as the breast cancer cells, probably due to the rapid cell division and higher iron concentration of leukemia cells. ("Selective cancer cell cytotoxicity from exposure to dihydroartemisinin and holotransferrin," Cancer Letters 91 {1995} 41-46)
These results were encouraging, but often test tube results do not carry over into animal testing, which was the next step.
The Rat Study
Rats that were implanted with cancer (fibrosarcoma) and given iron (ferrous sulfate) followed by a form of artemisinin (dihydroartemisinin) had a significant reduction in the growth rate of the implanted tumors. There appeared to be no tumor growth reduction in rats that were given either substance alone, iron or artemisinin. The researchers concluded in their abstract that "An artemisinin analog-ferrous salt combination may provide a novel approach for cancer therapy." ("Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted fibrosarcoma growth in the rat," Cancer Letters 98 {1995} 83-87)
Normally, at this point in research, the animal studies would be continued for several years with toxicity studies and further studies proving the efficacy of the protocol. Then small human studies would be started, again determining the toxicity levels and efficacy. This whole process takes years to complete before the general public would have access to this new treatment.
The development of this protocol has taken a different turn though, mainly due to the fact that artemisinin and its derivatives have been available and in use for 30 years, and have generally been considered safe and non-toxic (read toxicity information below). The herb itself has been used by the Chinese for many centuries. Dr. Lai has recognized a new use for a known substance.
Concern about Iron Supplementation
It is well known by physicians specializing in supportive nutritional cancer protocols that iron fuels cancer growth. Originally most physicians becoming aware of these published studies shied away from trying artemisinin if it required concurrent iron supplementation to work.
Dr. Singh says that cancers that have developed (not been implanted) in biological tissue usually have sequestered enough iron so that it is generally not necessary to take supplemental iron for the artemisinin to be effective. Dr. Singh started treating several cancer patients in India without an iron supplement and had observed a positive response.
Once physicians realized they did not have to give their patients iron to potentiate the artemisinin, several physicians started their terminal cancer patients on low doses. As word traveled through the cancer network, many patients who had exhausted all other options also initiated self-treatment with artemisinin. However, the possibility that concurrent intake of an iron supplement may enhance the effectiveness of artemisinin has not been further explored.
Early Success with Canine Osteosarcoma
Treatment with artemisinin was started on a dog with a bone cancer so severe it could not walk across the room. Within five days of treatment the dog was able to walk normally, and X-rays confirmed the disappearance of the tumor. Several dogs with lymphosarcoma had also been treated with artemisinin with an immediate reduction in tumor size. In all these canine cases, an iron supplement was used.
