Mimosine is a toxic nonprotein
amino acid that is a major constituent of the tropical legumes Leucaena and Mimosa.
Mimosine has been shown to cause acute and chronic toxicosis in livestock fed from forage containing these plants. Recently,
mimosine has been demonstrated to reversibly block cell cycle progression in mammalian cells in culture. In this study, we compared the effects of
mimosine to
desferrioxamine (DFO), a well-characterized
iron chelator, and found that both chemicals similarly altered cell cycle progression in MDA-MB-453 human
breast cancer cells.
Mimosine (400 microM) and DFO (150 microM) both reduced
DNA synthesis by greater than 90% of control within 4 hr of treatment, and suppressed total
proline-directed protein kinase activity to less than 10% of control after 16 hr treatment. These effects were antagonized by the addition of
iron as
ferrous sulfate (250 microM), which is bound to
transferrin and imported into the cell via
transferrin receptor endocytosis, or as
hemin (100 microM), which passes through the cell membrane and releases
iron into the cytosol. After 24 hr treatment with the
chelators, a large portion of the available
transferrin receptors moved to the cell surface, indicating that the cells were
iron-starved. Our data demonstrate that
mimosine, through
iron chelation, blocks cell cycle progression in MDA-MB-453 human
breast cancer cells.