Response of MCF-7 mamma carcinoma cells to glyoxal and methylglyoxal

Background:

The α-oxo-aldehydes glyoxal and methylglyoxal are byproducts of fatty acid oxidation and glycolysis. Cancer cells produce significantly more of these aldehydes than other cells due to their high glycolytic activity. These substances are highly reactive and modify proteins. As a result stable, accumulating products, the so called advanced glycation end products (AGEs)are formed. In this study we analysed the responses of the estrogen receptor positive mamma carcinoma cell line MCF-7 to glyoxal and methylglyoxal.

Methods:

Cell vitality was determined by the resazurin assay. Activation of MAP-kinases and NF-κB was determined by Western blotting. Oxidative stress was measured by loading the cells with the oxidation-sensitive fluorochrome dihydrofluorescein-diacetate.

Results:

Dialdehydes resulted in cell death in low millimolar concentrations. Cells exposed to the aldehydes responded by a rapid activation of MAP-kinase signalling and production of reactive oxygen species as well as activation of caspase 3/7 activity, finally leading to cell death. Interestingly, a tamoxifen resistant derivative of MCF-7 showed an additional activation of the NF-κB transcription factor by methylglyoxal only and was altogether more sensitive to the aldehydes. Addition of the antioxidant N-acetyl cystein protected the cells, demonstrating that oxidative stress was a major cause of cell death.

Conclusions:

These data demonstrate that exogenous aldehyde stress is cytotoxic to mamma carcinoma cells by causing severe oxidative stress. Inhibition of aldehyde defence enzymes such as glyoxalases might therefore be a promising therapeutic option against breast cancer.