Evaluation of Cytotoxic Effect L-Histidine Methyl Ester Hydrochloride of Amphotericin-B (A21) on Tumoral Cells

The term cancer encompasses a hundred diseases that are caused by damage and mutations in the genome. Damage to DNA can be caused by the increase of free radicals, which when interacting with nitrogenous bases and deoxyribose generate highly mutagenic products. The alterations in the genome trigger the activation and / or suppression of proteins that cause the cell to lose the regularization of the cell cycle and its capacity to induce apoptosis, which leads to an uncontrolled proliferation. Lung cancer is one of the leading causes of death worldwide, its main treatment is chemotherapy. Previous studies have shown that amphotericin B (AmB) has antineoplastic effects and potentiates the effect of other antineoplastics. L‐Histidyl methyl ester hydrochloride of amphotericin B (A21) is a derivative of AmB developed by researchers of the UAEM and UNAM. Preclinical studies have shown that the derivative has the same antifungal pharmacological efficacy, but less toxicity than AmB. Given that the AmB derivative is equally effective, but less toxic than the AmB, it is essential to know whether said derivative has the same antineoplastic capacity as its predecessor, and thus may be considered as an equally effective alternative treatment, but with a lower degree of toxic effects for the organism. Therefor, the aim of this work was to evaluate whether the derivative A21 produces cytotoxic effects in tumor cells. A549 cells (ATCC CCL‐185) were used: Non‐small cell lung carcinoma cells (Human). They are grown in supplemented F‐12 Ham Kainghn's Modification medium. The cells received the following treatments: cisplatin and AmB at 3, 7, 15 and 20 μg/mL and Derivative of AmB at 3, 7, 15, 30, 60 and 120 μg/mL. The evaluation of cytotoxicity was performed by an MTT assay. Cell morphology was assessed by Giemsa staining. Subsequently, a cell proliferation assay using MTT will be performed, oxidative stress will be evaluated (ROS‐GloTM H 2 O 2 ), and Caspase 8 and 9 levels will be quantified by means of a calorimetric assay. Inhibitory concentrations 50 (IC50) of each drug were obtained in which the cell viability was 50%. The IC 50 found were: cisplatin 20.6μg/mL, AmB 60 μg/mL and derivative AmB 121 μg/mL. When evaluating the morphology of the cells, it is observed that in the treatment with cisplatin at 7μg/mL increased the size of cells. The treatment with AMB and derivative A21 at the same concentration also increased the sizes of cells with more than 1 nucleus were also observed (compared with the control). Cells treated with The treatment with AmB and the derivative of A21 produced similar alterations in cell morphology than cisplatin. However, the IC50 were different for all treatments evaluated in A549 cells. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .