Materials/analysis tools: LJX FFZ. Wrote the paper: LJX YBL.Sensitivity evaluation of trials evaluating GFR alterations with newer vitamin D compounds therapy showed a low level of sensitivity. (TIF)Figure S
Int. J. Mol. Sci. 2013, 14, 16600-16616; doi:10.3390/ijmsOPEN ACCESSInternational Journal ofMolecular SciencesISSN 1422-0067 www.mdpi/journal/ijms ArticleCadmium Modifies the Cell Cycle and Apoptotic Profiles of Human Breast Cancer Cells Treated with 5-FluorouracilYolande Asara 1, Juan A. Marchal 2,three,*, Esther Carrasco 2,three, Houria Boulaiz 2,3, Giuliana Solinas 1, Pasquale Bandiera 1, Maria A. Garcia 4, Cristiano Farace 1, Andrea Montella 1 and Roberto Madeddu 1,five,*Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, Sassari 07100, Italy; E-Mails: [email protected] (Y.A.); [email protected] (G.S.); [email protected] (P.B.); [email protected] (C.F.); [email protected] (A.M.) Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Study, University of Granada, Granada E-18100, Spain; E-Mails: ecp_85@hotmail (E.C.); [email protected] (H.B.) Division of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Avda de Madrid s/n, Granada E-18100, Spain Oncology Department, University Hospital “Virgen de las Nieves”, Granada E-18100, Spain; E-Mail: mangelgarcia@ugr.Dantrolene es National Institut of Biostructures and Biosystems (INBB), viale delle Medaglie d’oro, Rome 00118, Italy* Authors to whom correspondence need to be addressed; E-Mails: [email protected] (J.A.M.); [email protected] (R.M.); Tel.: +34-958-249321 (J.A.M.); Fax: +34-958-246296 (J.A.M.); Tel./Fax: +39-79-228569 (R.M.). Received: 17 Might 2013; in revised type: 15 July 2013 / Accepted: 22 July 2013 / Published: 12 AugustAbstract: Industrialisation, the proximity of factories to cities, and human operate activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may well have deleterious effects on human well being. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, happen to be reported. 5-Fluorouracil (5-FU) is often a fluoropyrimidine anticancer drug used to treat solid tumours with the colon, breast, stomach, liver, and pancreas. The goal of this perform 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 had been greater when applied either alone or in mixture with 5-FU compared with 5-FU alone.Int.IL-1 beta Protein, Human J.PMID:24428212 Mol. Sci. 2013,Cd considerably suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Concerning gene and protein expression, bcl2 expression was mostly upregulated by all treatment options involving Cd. The expression of caspase eight and caspase 9 was decreased by a lot of the therapies and constantly evaluated. C-myc expression was improved by all remedies involving Cd, particularly 5-FU plus Cd at the half time of therapy. 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 benefits could have significant clinical implications in individuals treated with 5-FU-based therapies and that are exposed to high levels of Cd. Keywords: cadmium; 5-fluorouracil; MCF-7; breast cancer1. Introduction Industrialisation and alterations in human function activities have led to improved use of substances containing heavy meta.