Metallic compounds (arsenic trioxide and trimethyltin chloride) interact with calcium homeostasis and trigger cell death in “in vitro” systems

Abstract

AbstractWhile some metals are essential for normal cell function (e.g. zinc, selenium) others could be highly toxic (lead, mercury) and interestingly, some metallic species have dual effects being toxic and healing agents as well: e. g. arsenic trioxide (As2O3) is used to treat cancer but is also a classical carcinogen. While the mechanisms of interaction with living cells is not fully understood, we propose that the modification of intracellular calcium concentration ([Ca2+]i) induced by metallic compounds could be a main reason of cytotoxicity and/or apoptosis.Here we have compared the effects of two metal compounds (As2O3) and timethyltin chloride (TMT) on intracellular calcium ([Ca2+]i) homeostasis using “in vitro” cell models. Earlier experiments have shown that As2O3 and TMT modulate calcium signalling in tumour cells (human neuroblastoma, human cervix adenocarcinoma) as well as in non‐tumour cells (human embryonic kidney) by triggering calcium spikes as well as a sustained increase of [Ca2+]i. This increase was due to a release of Ca2+ from the intracellular calcium stores. Conclusion: metallic compounds like arsenic trioxide As2O3 and TMT interfere with calcium signals sharing some mechanism of action in living cells. In this mini‐overview we compare the effects of As2O3 and TMT on intracellular calcium homeostasis and we discuss possible common effects on triggering toxic effects.