Effects of the rare elements lanthanum and cerium on the growth of colorectal and hepatic cancer cell lines

Human HT-29 and HepG2 cell lines were employed to test the effects of increasing concentrations of two rare earth elements (REEs), namely cerium (Ce) and lanthanum (La), alone or in combination. Effects on cell proliferation were measured using MTT assay, luciferase-based assays and proliferating cell nuclear antigen expression, while cell mortality and type of cell death was determined by Annexin V-FTC test using flow cytometry. Modulation of 84 genes involved in oxidative stress pathways was also studied using RT-PCR based arrays. Major alterations in selected genes compared to basal expression levels of respective control groups were found in the cells exposed to 600μM Ce for 48h. In HepG2 cells, 51 out of 84 genes were significantly up- or down-regulated, while in HT-29 cells only 16 genes were significantly up- or down-regulated. Dosage of REEs seems to be the pivotal factor for switching the biological effects from down- to up-regulation of cell growth; thus, low concentrations promoted cell survival and proliferation, but when concentrations increased, REEs exerted anti-proliferative and cytostatic/cytotoxic effects. The molecular mechanisms underlying these effects are still not well-defined and further analysis of the mechanisms that result in inhibition or induction of cell proliferation are crucially important.