Authors: Sinikka Hinrichsen Britta PlanerFriedrich
Publish Date: 2016/01/18
Volume: 23, Issue: 9, Pages: 8349-8357
Abstract
Based on acute cytotoxicity studies selenosulfate SeSO3 − has been suggested to possess a generally higher toxic activity in tumor cells than selenite The reason for this difference in cytotoxic activity remained unclear In the present study cytotoxicity tests with human hepatoma HepG2 malignant melanoma A375 and urinary bladder carcinoma cells T24 showed that the selenosulfate toxicity was very similar between all three tested cell lines IC50 66–71 μM after 24 h It was largely independent of exposure time and presence or absence of amino acids What changed however was the toxicity of selenite which was lower than that of selenosulfate only for HepG2 cells IC50 15 μM but similar to and higher than that of selenosulfate for A375 IC50 47 μM and T24 cells IC50 35 μM respectively Addition of amino acids to T24 cell growth medium downregulated shortterm selenite uptake 15 versus 129 ng Se/106 cells and decreased its cytotoxicity IC50 84 μM rendering it less toxic than selenosulfate The suggested mechanism is a stronger expression of the xc − transport system in the more sensitive T24 compared to HepG2 cells which creates a reductive extracellular microenvironment and facilitates selenite uptake by reduction Selenosulfate is already reduced and so less affected The cytotoxic activity of selenosulfate and selenite to tumor cells therefore depends on the sensitivity of each cell line supplements like amino acids as well as the reductive state of the extracellular environmentWe acknowledge the generous funding by the German Research Foundation within the Emmy Noether program to B PlanerFriedrich grant no PL 302/31 and thank Franziska Geist for help in the laboratory Stefan Will for help with the AECICPMS analyses as well as Prof Dr Elke Dopp for providing us with HepG2 and T24 cells
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