Effect of Manganese Chloride and of Cotreatment with Cadmium Chloride on the In Vitro Proliferative, Motile, and Invasive Behavior of MDA-MB231 Breast Cancer Cells

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.

Manganese systemic distribution is modulated in vivo during tumor progression and affects tumor cell migration and invasion in vitro

“…We hypothesize that tumor cells able to retain Mn in vivo migrate more efficiently due to a more efficient integrin activation and collective migration behavior. Supporting evidence of this phenomenon has been described in an in vitro model of tumor cell migration, whereas MDA-MB-231 cells are exposed to MnCl 2 and monitored for migration and proliferation activities 48 . Findings show that MnCl 2 5 µM mainly stimulates transmigration through type I collagen (chemotaxis assay), while transmigration through matrigel (chemoinvasion assay) is more pronounced at MnCl 2 100 µM.…”

Transcriptome Analysis and SNP Identification Reveal That Heterologous Overexpression of Two Uncharacterized Genes Enhances the Tolerance of Magnaporthe oryzae to Manganese Toxicity

“…A downregulated gene that encodes separin has been reported to act as a protease to cleave a cohesion subunit and segregate chromosomes in anaphase ( 53 ). However, some cell cycle-related genes play dominant roles in tumorigenesis ( 54 ), and Mn complexes can exhibit anticancer activities ( 55 , 56 ). A recent result substantiated that Mn is essential in antitumor immune responses via the cGAS-STING pathway ( 57 ).…”

Micronutrient Status and Breast Cancer: A Narrative Review

“…Mn compounds are also associated with carcinogenic effects. Natural sources of manganese are cereals, whole grains, and nuts, but it can also be found in contaminated drinking water, thus increasing exposure in humans [174]. Human exposure to high concentrations of Mn in the environment may increase the risk of TNBC progression, while manganese superoxide dismutase (MnSOD) is thought to be a factor in tumor cell invasive activity [174].…”