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    Awarded Grants
    Artemisinin and Artemisinin-Tagged Transferrin for Prevention and Treatment of Breast Cancer

    Scientific Abstract:
    Research funding is being requested to investigate the possible use of artemisinin and related compounds for the treatment of breast cancer. Artemisinin is a compound isolated from the wormwood Artemisia annua L and has been used since the 1970s for the treatment of malaria infection in more than 2 millions patients. The artemisinin molecule contains an endoperoxide moiety (-C-O-O-C-) that can react with an iron atom to form a carbon-based free radical. Free radicals formed inside cells could cause cellular damages and lead to cell death. Cancer cells are more susceptible to the cytotoxic effect of artemisinin than normal cells because they pick up relatively large amount of iron to support their uncontrolled growth. In previous research, we have found that: (1) artemisinin, when provided with iron in culture, effectively killed human breast cancer cells, whereas its toxicity towards normal breast cells was minimal; (2) artemisinin given orally retarded the growth of implanted breast tumors in rats; and (3) oral administration of artemisinin could prevent and delay the development of breast cancer in rats. In addition, we have covalently tagged artemisinin to the iron-carrying protein transferrin. The assumption is that such an artemisinin-tagged compound would deliver both iron and artemisisnin in one package into cancer cells and would have higher selectivity and potency in killing cancer cells. We have found that the artemisinin-tagged compound is much more potent and selective in killing human breast cancer cells than normal breast cells in vitro compare to artemisinin alone. We will further explore the potential of artemisinin and artemisinin-tagged compounds as a new class of anti-cancer drugs. The aims of this proposed research are: a) to investigate the potency of artemisinin and the artemisinin-tagged compound in killing various types of human breast cancer cells in vitro, including those resistant to chemo- and radiation therapies; and b) to investigate in vivo the potency of the tagged-compound in retarding the growth of breast cancer in a rat model. Artemisinin has been shown to be safe when taken orally and have little side effect. It can be produced economically either by extraction from wormwood plant or by using recombinant method. Thus, it can be developed to be an effective, easily administered, and economical treatment for breast cancer. On the other hand, the artemisinin-tagged compound would be a more effective but expensive treatment. However, it can also be easily administered to patients as an aerosol inhalant.

    Lay Abstract:
    The goal of this proposed research is to investigate the anticancer potency of artemisinin, a natural compound isolated from the sweet wormwood Artemisia. A unique feature of artemisinin is that it can react with an iron atom to form a free radical. Free radicals formed inside cells could cause cell death. Cancer cells are more susceptible to the toxic effect of artemisinin than normal cells because they pick up relatively large amount of iron to support their uncontrolled growth. Indeed, artemisinin has been shown to selectively kill human breast cancer cells with little harmful effect on normal breast cells, retard the growth of breast tumors, and prevent or delay the development of breast cancer in rats. The advantages of artemisinin are that it is nontoxic, cheap and can be taken orally. To further investigate the potency of artemisinin as a breast cancer treatment drug, we propose to study the potency of artemisinin in killing various types of human breast cancer cells that are either resistant to radiation or chemotherapeutic agents. Based on the artemisinin molecule, we have synthesized a compound that is more potent and specific in killing cancer cells than artemisinin. Another goal of this proposed research is to further investigate the potency of this synthetic compound on various types of human breast cancer cells and to test it on animals. This compound also can be easily administered to humans in an aerosol inhalant. Artemisinin could be a potential breast cancer treatment for women in developing countries where traditional therapies are too expensive or inaccessible, since it is inexpensive, can be taken orally, and has no side effect. The new synthetic compound, though more effective than artemisinin, is much more expensive. However, future technological developments, such as recombinant technique, may possibly lower the cost of this compound and make it available to all breast cancer patients. The anticancer property of artemisinin and the synthetic compound is not only limited to breast cancer. Their mode of action suggests that they may be useful in the treatment of many other forms of cancer. In addition to breast cancer, we have also found that they are effective against leukemia.