Common Pathway for K562 Cells Endocytosis and Release of Gac-Tf and Ga2-Tf via a Transferrin Receptor

There has been an increasing interest in the use of gallium in anticancer activity. However, whether the uptakes of two species of transferrin, including digallium transferrin (Ga₂‐Tf) and the C‐terminal monogallium transferrin (Ga_C‐Tf) by cells, are different is not well understood. In this work the mechanism of both species passing in and out K562 cells has been established by using ¹²⁵I‐labeled transferrin. There were about (1.5±0.08)×10⁵ binding sites per cell surface. Both Ga₂‐Tf and Ga_C‐Tf were recycled to the cell exterior with a protracted endocytic cycle compared to apotransferrin (apoTf). The cycling time from the internalization to release was calculated about t_1/2= (3.15±0.055) min for apoTf, t_1/2= (4.69±0.09) min for Ga₂‐Tf and t_1/2= (4.78±0.15) min for Ga_C‐Tf. The result implies that metal dissociating from transferrin in acidic endosomes was likely to be the key step. Both Ga₂‐Tf and Ga_C‐Tf into K562 cells are transferrin receptor‐mediated process with a similar rate of endocytosis and release. Our present observations provide useful information for better targeted drugs in specific therapy.