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

Journal of Experimental & Clinical Cancer Research

Michele Caraglia¹  Nicola Sannolo²  Annamaria Spina¹  Silvio Naviglio¹  Delia Pesce¹  Daniela Feola²  Anna Grimaldi¹  Silvia Zappavigna¹  Monica Marra¹  Stefania Porto¹  Monica Lamberti² 

[1] Department of Biochemistry and Biophysics, Second University of Naples, Via S.M. Costantinopoli, 16, 80138, Naples, Italy;Occupational Medicine, Hygiene and Industrial Toxicology Section, Department of Experimental Medicine, Naples, Italy

关键词: Health workers;    Cardiotoxicity;    ROS;    Apoptosis;    Doxorubicin;    5-Fluorouracil;   

Others  :  826260
DOI  :  10.1186/1756-9966-31-60

 received in 2012-06-20, accepted in 2012-07-19,  发布年份 2012

【 摘 要 】

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 (5–7% 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.

【 授权许可】

   
2012 Lamberti et al.; licensee BioMed Central Ltd.

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