Aim: 

Cadmium (Cd) is a heavy metal present in tobacco smoke and contaminated industrial soils and it has been recently considered as a human carcinogen. Metallothioneins (MTs) are ubiquitous proteins essential for cell protection. The toxic effects of cadmium can be modified by compounds able to modulate metallothionein synthesis. Melatonin (Mel), the pineal hormone, has antiestrogenic as well as antioxidant properties, and has also been shown to counteract the toxic effects of the heavy metal. Therefore, our objective was to examine the possible role of melatonin in cadmium-induced expression of several metallothionein isoforms (MT-2A, MT-1X, MT-1F, MT-1E) in three human tumor cell lines (MCF-7, MDA-MB-231 breast cancer cells and HeLa cells).

Methods: 

MCF-7, HeLa and MDA-MB-231 cells were cultured in media with estrogen-depleted serum and treated with 1 mM CdCl₂, 100 nM Mel or CdCl₂ + melatonin. After 2 hours of incubation the cells were lysated and mRNA were extracted to measure metallothionein gene expression by real time PCR assay (QPCR).

Results: 

We found that in all cell types, melatonin increases cadmium-induced expression of MT-2A, which is considered to protect against cadmium toxicity. As regards, MT-1 subtypes, which have been related with cell invasiveness and high histological grade tumors, melatonin decreased cadmium-induced expression in both breast cancer cell lines but the opposite effect was found in HeLa cells.

Conclusion: 

The effects of melatonin on MT-2A expression point towards this indolamine's possible role as a preventive agent for carcinogenesis dependent on environmental or occupational cadmium contamination.

Supported by the Spanish MCYT (SAF2007-60659 and 62762).