Effect of CaS Nanostructures in the Proliferation of Human Breast Cancer and Benign Cells In Vitro

Abstract

We report on the effect of naked CaS nanostructures on the proliferation of carcinoma cancer cells and normal fibroblasts in vitro. The CaS nanostructures were prepared via the microwave-mediated decomposition of dimethyl sulfoxide (DMSO) in the presence of calcium acetate Ca(CH3CO2)2. Light scattering measurements revealed that dispersions contain CaS nanostructures in the size range of a few Å to about 1 nanometer, and are formed when DMSO is decomposed in the presence of Ca(CH3CO2)2. Theoretical calculations at the DFT/B3LYP/DGDZVP level of theory on (CaS)n clusters (n = 1, 2, 3, and 4) are consistent with clusters in this size range. The absorption spectra of the CaS nanostructures are dominated by strong bands in the UV, as well as weaker absorption bands in the visible. We found that a single dose of CaS nanoclusters smaller than 0.8 nm in diameter does not affect the survival and growth rate of normal fibroblasts and inhibits the proliferation rate of carcinoma cells in vitro. Larger CaS nanostructures, approximately (1.1 ± 0.2) nm in diameter, have a similar effect on carcinoma cell proliferation and survival rate. The CaS nanoclusters have little effect on the normal fibroblast cell cycle. Human carcinoma cells treated with CaS nanocluster dispersion exhibited a decreased ability to properly enter the cell cycle, marked by a decrease in cell concentration in the G0/G1 phase in the first 24 h and an increase in cells held in the SubG1 and G0/G1 phases up to 72 h post-treatment. Apoptosis and necrotic channels were found to play significant roles in the death of human carcinoma exposed to the CaS nanoclusters. In contrast, any effect on normal fibroblasts appeared to be short-lived and non-detrimental. The interaction of CaS with several functional groups was further investigated using theoretical calculations. CaS is predicted to interact with thiol (R-SH), hydroxide (R-OH), amino (R-NH2), carboxylic acid (R-COOH), ammonium (R-NH3+), and carboxylate (R-COO−) functional groups. None of these interactions are predicted to result in the dissociation of CaS. Thermodynamic considerations, on the other hand, are consistent with the dissociation of CaS into Ca2+ ions and H2S in acidic media, both of which are known to cause apoptosis or cell death. Passive uptake and extracellular pH values of carcinoma cells are proposed to result in the observed selectivity of CaS to inhibit cancer cell proliferation with no significant effect on normal fibroblast cells. The results encourage further research with other cell lines in vitro as well as in vivo to translate this nanotechnology into clinical use.

pH-Selective Reactions to Selectively Reduce Cancer Cell Proliferation: Effect of CaS Nanostructures in Human Skin Melanoma and Benign Fibroblasts

“…We conclude that the 3% CaS dispersions reduce the viability of melanoma cells with little effect on the viability of corresponding benign cells. The results are consistent with our earlier observations on human lung and breast cancer cell lines, where the CaS nanostructures reduce malignant cell proliferation with little or no effect on corresponding benign cells [ 15 – 18 ].…”

“…The overall results are consistent with our general hypothesis that CaS selectively dissociates in the acidic extracellular environment found in cancer cells—including lung, breast, and skin malignant tumors—but not in the fluid of corresponding benign cells [ 18 ]. The reader is referred to Figure 7 to facilitate the following discussion that represents our interpretation of a possible pathway to account for the observed results.…”