Abstract A08: Cadmium elicits a differential cytotoxic response in triple-negative breast cancer cells

Abstract

Abstract Understanding the relationship between heavy metal exposure and triple-negative breast cancer cells may help to elucidate the high breast cancer mortality rate and health disparity in African-American women, as they may be exposed to these heavy metals at higher rates when compared to their Caucasian counterparts. Triple-negative breast vancer (TNBC) accounts for about 15% of all breast cancers and is characterized by cancer cells that lack the expression of estrogen, progesterone, and HER2/Neu receptors. For this reason, TNBC cells do not respond to hormone therapies or HER2/Neu-targeted treatments. The human body utilizes some metals in small amounts as micronutrients; however, metals such as cadmium-2 that are introduced to the body are not needed physiologically. Human exposure to trace metals in higher-than-needed amounts or exposure to nonessential metals can cause damage to the body as they can be toxic or even carcinogenic. Here we expose the TNBC cell lines HCC 1806 and HCC 70 to cadmium-2. While less is known about the long-term carcinogenic potential of cadmium exposure in the broader population and for other organs, evidence suggests its potential association to lung, breast, and endometrial cancer and mortality. Previous lab data revealed that exposure to high concentrations of cadimum-2 ions causes a differential cytotoxic cell death response in TNBC cells and demonstrates different genotoxic targets and implications in their mutagenic potential when HCC 1806 and HCC 70 cell lines were exposed to this ion. Here, the cell lines have been treated with 5 ug/ml of cadmium-2 ion, revealing increased toxicity using the lactate dehydrogenases assay (LDH), decreased viability (MTS assay), and flow cytometry reveals an abrogation of the cell cycle. The LDH assay revealed that the cells exposed to cadmium resulted in a P-value less than 0.0001 and assay data present percent cytotoxicity of 14.13 and 12.58, respectively, for control and treated cells. A similar trend was exhibited in HCC 70, where the LDH assay resulted in a p-value less than 0.0001 and assay data demonstrated a percent cytotoxicity of 11.57 and 6.92, respectively, for control and treated cells. The MTS assay alongside trypan blue exclusion assay demonstrated a trend of decreasing viability among the treated cells. The flow cytometric analysis revealed an increase in the S-phase in the cadmium-treated cells compared to the controls. These results are potentially early indicators of a molecular effect of Cd ions on breast cancer cells that could elucidate the role that cadmium may play in promoting the aggressive behavior of TNBC or could potentially lead to future treatment regimens. Citation Format: Sherette Godfrey, Checo Rorie. Cadmium elicits a differential cytotoxic response in triple-negative breast cancer cells [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A08.