Amphotericin A21 Induces Cytotoxic Effects in Breast Cancer Cell Lines

Abstract

INTRODUCTIONCancer is a public health problem that causes enormous loss of human life. Worldwide, breast cancer is one of the most diagnosed types of cancer and one that contributes significantly to cancer mortality. One of the situations that contributes to mortality statistics is that the patient may present low efficacy to treatment or the development of resistance. Currently there are various antineoplastic drugs, but these are not enough to face the complications of the disease. Therefore, it is of interest to study new drugs that have antineoplastic potential. Amphotericin B L‐histidine methyl ester, known as Amphotericin A21 (AmB‐A21), is a compound that has been extensively studied by our research group. Toxicological studies have shown that AmB‐A21 is a very safe compound, causing little toxicity in in vivo models. AmB‐A21 has also been found to have a cytotoxic effect, induce apoptosis, and reduce the proliferation and invasion of lung cancer cells (A549 cells). The results of the evaluations suggest that AmB‐A21 has the potential to be an effective and safe antineoplastic drug. The present project aims to evaluate whether AmB‐A21 can also cause antineoplastic effects in breast cancer cell lines, first evaluating the cytotoxic effect of AmB‐A21.AIMTo evaluate the cytotoxic effect of AmB‐A21 on MDA‐MB‐231 and MCF7 cells.HYPOTHESISAmB‐A21 induces cytotoxicity in MDA‐MB‐231 and MCF7 cells.MethodsMDA‐MB‐231 (ATCC HTB‐26) and MCF‐7 (ATCC HTB‐22) lines from breast cancer were used. Both lines were cultured at 37 ° C, with 5% CO2, in DMEM HG medium supplemented with non‐essential amino acids, glutamine, sodium pyruvate, gentamicin and 10% fetal bovine serum.First, growth kinetics were performed for 72 hours (h), to characterize the doubling rate and time of each cell line. Subsequently, dose‐response curves were performed to evaluate the cytotoxic effect of AmB‐A21 and inhibitory concentrations 50 (IC50) were calculated. Finally, the type of cell death that AmB‐A21 induces at IC25 y 50 was identified in MCF‐7 cells.RESULTSThe proliferation rate at 72 h was found to be 2.43 ± 0.38 and 3.10 ± 0.21 for MDA‐MB‐231 and MCF‐7 cells respectively. Regarding the dose‐response curves, it was found that AmB‐A21 induces a concentration‐dependent cytotoxic effect in both breast cancer cell lines, whose IC50 were 178.83 ± 18.8 and 207.24 ± 5.7 µM/mL for the MDA‐MB‐231 and MCF‐7 cells, respectively. The results obtained had a statistically significant difference, with respect to the control. Data are shown as mean ± standard deviation. AmB‐A21 was also found to induce apoptosis cell death in MCF‐7 cells with their IC50 & 25.CONCLUSIONSAmB‐A21 induces cytotoxicity in cell lines originating from breast cancer (MDA‐MB‐231 and MCF‐7) and generates cell death by apoptosis in MCF‐7 cells.