Cadmium Modifies the Cell Cycle and Apoptotic Profiles of Human Breast Cancer Cells Treated with 5-Fluorouracil

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.

Epigenetic marks responsible for cadmium-induced melanoma cell overgrowth

“…Indeed, the employment of high-dose TNFa locally administered in combination with liposomal drugs has been approved for treatment in patients with in transit metastatic melanoma (Eggermont et al, 2003;van Horssen et al, 2006). Moreover, our data extend early in vitro and in vivo observations linking exposure to Cd with decreased expression of caspase 8 in tumors different from melanoma (Asara et al, 2013;Gunawardana et al, 2006). The pivotal role of caspase 8 overexpression in reactivating the apoptosis program in cutaneous melanoma cells exposed to Cd with hypermethylated caspase 8 promoter (Fig.…”

Higher expression of SATB2 in hepatocellular carcinoma of African Americans determines more aggressive phenotypes than those of Caucasian Americans

“…The Western blot analysis was performed as we described earlier. 23 In brief, cells were washed once with ice-cold PBS and suspended in RIPA lysis buffer (10 mM Tris-HCl, pH 7.4, 140 mM NaCl, 1% Triton X-100, 1% Sodium deoxycholate, 0.1% SDS, 1 mM Na 3 VO 4 , 1 mM NaF and 1 mM EDTA) added with a cocktail of protease inhibitors. Lysis was performed on ice for 30 minutes, and the samples were centrifuged at 17 000 g for 30 minutes.…”

Removal of Aquatic Cadmium Ions Using Thiourea Modified Poplar Biochar

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