Artemisinin™ is an extract of Artemisia annua, a plant that is also called Chinese Wormwood. Artemisinin was discovered as the active component of Artemisia annua in the early 1970s, and the leaf flavonoids from this plant, contained in many traditional Chinese herbal preparations, have shown a wide variety of biological activities against malaria and cancer.
In the Netherlands, Artemisinin is prepared as food supplement; however, the manufacturing process follows international standards for the production of pharmaceuticals.
Artemisinin is frequently used by patients with parasitic infections; in particular Malaria. The anti-Malaria efficacy of artemisinin has been recognized by the WHO and is reflected in the recommended use of artemisinin and its semi-synthetic analogs, such as dihydroartemisinin, artemether, arteether, and artesunate for otherwise treatment-resistant strains of Malaria. In the last decade, however, more and more scientific work has shown that artemisinin exerts also very potent anti-cancer effects. Today, many cancer patients utilize artemisinin in combination with their conventional therapy for added benefit in their fight against cancer.
Recently, it also has been suggested that artemisinin and its semi-synthetic analogs might become even more effective in the treatment of parasitic diseases (such as malaria) and cancer, if simultaneously administered with flavonoids. The flavonoids present in Artemisia annua leaves have been linked to suppression of CYP450 enzymes responsible for altering the absorption and metabolism of artemisinin in the body, but also have been linked to a beneficial immune-modulatory activity in subjects afflicted with parasitic and chronic diseases. The pleiotropic response towards artemisinin in cancer cells includes growth inhibition by cell cycle arrest, stimulation of apoptosis, inhibition of angiogenesis, disruption of cell migration, and modulation of nuclear receptor responsiveness.
Artemisinin also contains an endoperoxide moiety that reacts with intracellular iron to form cytotoxic free radicals. Cancer cells are known to contain a significantly higher free iron concentration than normal cells (almost factor of 1000), and it has been shown that artemisinin and its analogs exert a selective stimulation of apoptosis in many cancer cell lines. Cancer cells express a high concentration of transferrin receptors on their cell surface that facilitate uptake of the iron-carrying protein transferrin from the plasma via endocytosis. By tagging artemisinin to transferrin, artemisinin will be selectively picked up and concentrated in cancer cells and both, artemisinin and iron, would be transported into the cell in one package. Once such artemisinin-tagged transferrin molecule is endocytosed, iron will be released within the cancer cell and react with artemisinin moieties tagged to transferrin. The free radicals that are formed in that process can kill the cancer cell. Presently, potent and target-selective artemisinin-compounds are being developed, including artemisinin dimers and trimers, artemisinin hybrids, and artemisinin compounds that are bound to molecules involved in the intracellular iron-delivery mechanism. All these compounds are promising and potent anticancer compounds that probably have significantly less side effect than traditional chemotherapeutic agents.
Moreover, artemisinin has significant anti-angiogenic, anti-inflammatory, and anti-metastatic effects. Therefore artemisinin compounds are attractive cancer chemotherapeutic drug candidates, however, artemisinin and its analogs have short plasma half-lives, and require high dosages and frequent administration to be effective for cancer treatment.
Artemisinin is a very promising anti-cancer drug candidate. It is well tolerated, and in doses up to 50mg per kg body weight, practically without side effects. However, it has a short half-life and its bioavailability reduces rather quickly when taken orally due to reduced absorption through the intestinal wall. Nevertheless, given within the frame work of a suitable treatment protocol, artemisinin can provide significant benefits to cancer patients.
Artemisinin has the following effects:
- It creates selective cytotoxic effects in various cancer cells due to free radical generation (cancer cell time bomb) when reacting with the high iron concentration found in cancer cells.
- It causes a dose- and time-dependent G1 cell cycle arrest in various cancer cells which is not depending on its ability to create free radical toxicity.
- It causes dose- and time dependent cell cycle arrest (G1 phase) in androgen-responsive as well as in androgen-unresponsive prostate cancer cell cultures.
It has significant anti-angiogenic effects in animal models of with transplanted cancers, including prostate cancer; it reduces primary tumor growth and growth of metastases.