Interaction of manganese(II) complex with apotransferrin and the apotransferrin enhanced anticancer activities

Abstract

Apotransferrin could bind a number of metal ions besides Fe, which makes it an attractive delivery vehicle for metal-based medicines. In order to evaluate whether anticancer Mn(II) complex of [(Adpa)Mn(Cl)(H(2)O)] Adpa=bis(2-pyridylmethyl)amino-2-propionic acid) (AdpaMn) could be transported by apotransferrin, we investigated its interaction with human apotransferrin by fluorescence and circular dichroism spectroscopy (CD). The association dynamics show that AdpaMn could bind to apotransferrin spontaneously in Hepes buffer. Synchronous fluorescence spectroscopy and CD spectroscopy show that the conjugation of AdpaMn and apotransferrin by hydrophobic interactions induces the change of the microenvironment and conformation of apotransferrin. The reversible binding and release of AdpaMn was studied with fluorescence titration method. The AdpaMn complex can be released from the AdpaMn-apotransferrin entity in weak acid environments. MTT assay in vitro confirms that apotransferrin can enhance the inhibition rate of AdpaMn on the proliferation of HepG-2 cells, so we deduce that AdpaMn could be transported by apotransferrin in vivo.