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Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil

Asara, Yolande and Marchal, Juan A. and Carrasco, Esther and Boulaiz, Houria and Solinas, Maria Giuliana and Bandiera, Pasquale and García, María Angeles and Farace, Cristiano and Montella, Andrea Costantino Mario and Madeddu, Roberto Beniamino (2013) Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil. International Journal of Molecular Sciences, Vol. 14 (8), p. 16600-16616. eISSN 1422-0067. Article.

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DOI: 10.3390/ijms140816600

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Abstract

Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd.

Item Type:Article
ID Code:9644
Status:Published
Refereed:Yes
Uncontrolled Keywords:Cadmium, 5-fluorouracil, MCF-7, breast cancer
Subjects:Area 05 - Scienze biologiche > BIO/17 Istologia
Area 06 - Scienze mediche > MED/01 Statistica medica
Area 05 - Scienze biologiche > BIO/16 Anatomia umana
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Publisher:Molecular Diversity Preservation International
eISSN:1422-0067
Copyright Holders:© 2013 by the authors; licensee MDPI
Deposited On:26 Feb 2014 09:57

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