In vitro evaluation of the antitumor effect of bismuth lipophilic nanoparticles (BisBAL NPs) on breast cancer cells

Rene Hernandez-Delgadillo,1 Claudia María García-Cuéllar,2 Yesennia Sánchez-Pérez,2 Nayely Pineda-Aguilar,3 Marco Antonio Martínez-Martínez,1 Eyra Elvyra Rangel-Padilla,1 Sergio Eduardo Nakagoshi-Cepeda,1 Juan Manuel Solís-Soto,1 Rosa Isela Sánchez-Nájera,1 María Argelia Akemi Nakagoshi-Cepeda,1 Shankararaman Chellam,4 Claudio Cabral-Romero1 1Universidad Autónoma de Nuevo León, UANL, Facultad de Odontología, Laboratorio de Biología Molecular, Monterrey, Nuevo León, México; 2Subdirección de Investigación Básica, Instituto Nacional de Cancerología, CDMX, México; 3Centro de Investigación en Materiales Avanzados, S.C. (CIMAV), Unidad Monterrey, Nuevo León, México; 4Texas A&M University, College Station, TX, USA Aim: The objective of this study was to evaluate the antitumor activity of lipophilic bismuth nanoparticles (BisBAL NPs) on breast cancer cells.Materials and methods: The effect of varying concentrations of BisBAL NPs was evaluated on human MCF-7 breast cancer cells and on MCF-10A fibrocystic mammary epitheliocytes as noncancer control cells. Cell viability was evaluated with the MTT assay, plasma membrane integrity was analyzed with the calcein AM assay, genotoxicity with the comet assay, and apoptosis with the Annexin V/7-AAD assay.Results: BisBAL NPs were spherical in shape (average diameter, 28 nm) and agglomerated into dense electronic clusters. BisBAL NP induced a dose-dependent growth inhibition. Most importantly, growth inhibition was higher for MCF-7 cells than for MCF-10A cells. At 1 µM BisBAL NP, MCF-7 growth inhibition was 51%, while it was 11% for MCF-10A; at 25 µM BisBAL NP, the growth inhibition was 81% for MCF-7 and 24% for MCF-10A. With respect to mechanisms of action, a 24-hour exposure of 10 and 100 µM BisBAL NP caused loss of cell membrane integrity and fragmentation of tumor cell DNA. BisBAL NPs at 10 µM were genotoxic to and caused apoptosis of breast cancer cells.Conclusion: BisBAL NP-induced growth inhibition is dose dependent, and breast cancer cells are more vulnerable than noncancer breast cells. The mechanism of action of BisBAL NPs may include loss of plasma membrane integrity and a genotoxic effect on the genomic DNA of breast cancer cells. Keywords: antitumor activity, bismuth nanoparticles, breast cancer, chemotherapy, cytotoxicity