Abstract
We examined the dose–response effect of MnCl2 on the proliferative behavior of triple-negative breast cancer MDA-M231 cells vs. immortalized HB2 cells from breast epithelium taken as nontumoral counterparts. We also tested the effect of MnCl2 on tumor cell invasiveness in vitro by evaluating the relative invasion indexes through Boyden chamber assays. Moreover, we checked whether cotreatment with both MnCl2 and CdCl2 could modify the observed biological response by MDA-MB231 cells. Our results show a promotional impact of MnCl2 on cell proliferation, with 5 µM concentration inducing the more pronounced increase after 96-h exposure, which is not shared by HB2 cells. Exposure to 5 µM MnCl2 induced also an elevation of the relative invasion index of cancer cells. The Mn-mediated stimulatory effects were counteracted by cotreatment with CdCl2. These data support the concept that human exposure to high environmental concentrations of Mn may increase the risk of carcinogenesis and metastasis by prompting the expansion and dissemination of triple-negative breast cancer cells. On the other hand, the Mn-counteracting anticancer property of Cd looks promising and deserves a more detailed characterization of the involved intracellular targets aimed to the molecular modeling of specific antineoplastic agents against malignant breast cancer spreading.
Highlights
Manganese (Mn) is a natural occurring element in the earth’s crust where it represents the twelfth most abundant one
In the first set of assays we checked the effect of exposure to increasing concentrations of MnCl2 for various time lapses on the proliferative behavior of MDA-MB231 Triple-negative breast cancers (TNBC) cells via crystal violet assay
The dose–time response pattern after exposure to 100 μM MnCl2 was symptomatic of a viability- and growth-restraining activity exerted by the molecule at this high concentration on the breast cancer cell line
Summary
Manganese (Mn) is a natural occurring element in the earth’s crust where it represents the twelfth most abundant one. It is not found in nature as a pure metal but as a component of several inorganic and organic compounds. The major implementations of Mn include steel production and the alloying of aluminum. The major dietary source of Mn for humans is vegetables, e.g., cereals, whole grain, and nuts, and usually Mn intake from food is higher than that from water. Since the environmental concentration of the metal may be elevated by anthropogenic activities such as industrial emissions, fossil fuel combustion, and use of pesticides, this can result in its release into and contamination of drinking water with consequent increase of human exposure. Mn uptake by mammalian cells is mediated by different transporters, such as the divalent metal transporter -1 (DMT-1) and Zrt- and Irt-like proteins (ZIP) 8 and 14 [3,4], which show affinity for other divalent metals, i.e., cadmium (Cd) and zinc (Zn)
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