Artemisinin reacts with
iron to form
free radicals that kill cells. Since
cancer cells uptake relatively large amount of
iron than normal cells, they are more susceptible to the toxic effect of
artemisinin. In previous research, we have shown that
artemisinin is more toxic to
cancer cells than to normal cells. In the present research, we covalently attached
artemisinin to the
iron-carrying plasma
glycoprotein transferrin.
Transferrin is transported into cells via receptor-mediated endocytosis and
cancer cells express significantly more
transferrin receptors on their cell surface and endocytose more
transferrin than normal cells. Thus, we hypothesize that by tagging
artemisinin to
transferrin, both
iron and
artemisinin would be transported into
cancer cells in one package. Once inside a cell,
iron is released and can readily react with
artemisinin close by tagged to the
transferrin. This would enhance the toxicity and selectivity of
artemisinin towards
cancer cells. In this paper, we describe a method to synthesize such a compound in which
transferrin was conjugated with an analog of
artemisinin artelinic acid via the N-
glycoside chains on the C-domain. The resulting conjugate ('tagged-compound') was characterized by MALDI-MS, UV/Vis spectroscopy, chemiluminescence, and HPLC. We then tested the compound on a human
leukemia cell line (Molt-4) and normal human lymphocytes. We found that
holotransferrin-tagged
artemisinin, when compared with
artemisinin, was very potent and selective in killing
cancer cells. Thus, this 'tagged-compound' could potentially be developed into an effective chemotherapeutic agent for
cancer treatment.