Malignant H1299 tumour cells preferentially internalize iron-bound inositol hexakisphosphate

In colon enterocytes and in well-differentiated colon cancer CaCo-2 cells, InsP(6) (inositol hexakisphosphate) inhibits iron uptake by forming extracellular insoluble iron/InsP(6) complexes. In this study, we confirmed that CaCo-2 cells are not able to take up iron/InsP(6) but, interestingly, found that the cells are able to internalize metal-free and Cr(3+)-bound InsP(6). Thus, the inability of CaCo-2 cells to take up iron/InsP(6) complexes seems to be due to the iron-bound state of InsP(6.) Since recently we demonstrated that the highly malignant bronchial carcinoma H1299 cells internalize and process InsP(6,) we examined whether these cells may be able to take up iron/InsP(6) complexes. Indeed, we found that InsP(6) dose-dependently increased uptake of iron and demonstrated that in the iron-bound state InsP(6) is more effectively internalized than in the metal-free or Cr(3+)-bound state, indicating that H1299 cells preferentially take up iron/InsP(6) complexes. Electron microscope and cell fraction assays indicate that after uptake H1299 cells mainly stored InsP(6)/iron in lysosomes as large aggregates, of which about 10% have been released to the cytosol. However, this InsP(6)-mediated iron transport had no significant effects on cell viability. This result together with our finding that the well-differentiated CaCo-2 cells did not, but the malignant H1299 cells preferentially took up iron/InsP(6,) may offer the possibility to selectively transport cytotoxic substances into tumour cells.