5-Fluorouracil induces apoptosis in rat cardiocytes through intracellular oxidative stress

Background: cardiotoxicity is a major complication of anticancer drugs,including anthracyclines and 5-fluorouracil (5-fu) and it can have detrimental effects both in patients and workers involved in the preparation of chemotherapy. methods: specifically,we have assessed the effects of increasing concentrations of 5-fu and doxorubicin (doxo) on proliferation of h9c2 rat cardiocytes and ht-29 human colon adenocarcinoma cells by mtt assay. cells were treated for 24,48 and 72 h with different concentrations of the two drugs alone or with 5-fu in combination with 10-4 m of levofolene (lf). results: 5-fu induced a time- and dose-dependent growth inhibition in both cell lines. the 50% growth inhibition (ic:50) was reached at 72 h with concentrations of 4 μm and 400 μm on ht-29 and h9c2,respectively. the addition of lf to 5-fu enhanced this effect. on the other hand,the ic:50 of doxo was reached at 72 h with concentrations of 0.118 μm on h9c2 and of 0.31 μm for ht-29. we have evaluated the cell death mechanism induced by 50% growth inhibitory concentrations of 5-fu or doxo in cardiocytes and colon cancer cells. we have found that the treatment with 400 μm 5-fu induced apoptosis in 32% of h9c2 cells. this effect was increased by the addition of lf to 5-fu (38% of apoptotic cells). apoptosis occurred in only about 10% of ht-29 cells treated with either 5-fu or 5-fu and lf in combination. doxo induced poor effects on apoptosis of both h9c2 and ht-29 cells (57% apoptotic cells,respectively). the apoptosis induced by 5-fu and lf in cardiocytes was paralleled by the activation of caspases 3,9 and 7 and by the intracellular increase of o2? levels. conclusions: these results suggest that cardiotoxic mechanism of chemotherapy agents are different and this disclose a new scenario for prevention of this complication. © 2012 voutsadakis; licensee biomed central ltd.