EVALUATION OF ANTITUMORAL EFFECT OF THE COMBINATION OF L‐HISTIDINE METHYL ESTHER HYDROCHLORIDE OF ANFOTERICIN B WITH ANTINEOPLASTICS ON A549 CELLS
Authors: Escobar-Reséndiz Rubi , Reyes-Esparza Jorge , Blake Ivan Ortega , Rodriguez-Fragoso Lourdes 
Published: April 2020

Lung cancer is the leading cause of death, due to cancer, in the world. Performing an adequate and timely treatment in the patient can be complicated for the following reasons: the diagnosis of the disease is late delaying the application of treatment, the level of response to treatment is poor, in addition frequently develop resistance to treatment. Previous studies have detected that amphotericin B (AmB) has antineoplastic effects and enhances the effect of other antineoplastic drugs. L‐Histidine Methyl Ester Hydrochloride of AmB (A21) is a derivative of AmB developed by academics of the UAEM and UNAM. Previous preclinical studies have shown that derivative A21 has the same antifungal efficacy and is not toxic compared to AmB. Since derivative A21 is not toxic and is as effective as AmB, it is important to know if the derivative produces the same antineoplastic effects as its precursor, and can be considered as an alternative treatment as effective, but with less toxic effects in the organism. To assess whether derivative A21 has antitumor effects and produce pharmacological interactions with antineoplastic drugs in vitro. A549 cells (ATCC CCL‐185) were used: non‐small cell lung carcinoma cells (Human). They were grown in supplemented F‐12K medium. The cells received the following treatments: cisplatin, carboplatin, AmB, A21, cisplatin+AmB, cisplatin+A21, carboplatin+AmB, carboplatin+AmB. Cytotoxicity and cell proliferation were evaluated using the MTT technique. The type of cell death was identified by staining with ethidium bromide and acridine orange. The DNA damage assessment (HSC DNA Damage kit) and the effect on cellular invasive capacity were performed. In each individual drug 25 inhibitory concentrations (IC25) were obtained in which the cell viability was 75%. The IC25 found were: cisplatin 10μg/ml, carboplatin 515μg/ml, AmB 29μg/ml and A21 derivative 67μg/ml, these concentrations were used to make the combinations. In the evaluation of cytotoxicity and proliferation it was observed that the cisplatin+A21 combination reduced approximately 40 and 70% approximately viability and proliferation rate respectively, while carboplatin+A21 treatment reduced approximately 50 and 95%, on the other hand, the A21 treatment reduced the proliferation rate by 40% compared to the control. It was identified that treatments A21, cisplatin+A21 and Carboplatin+A21 induced apoptosis death in approximately 45, 75 and 80% of cells, respectively. In the invasion test it was obtained that treatments A21, cisplatin+A21 and Carboplatin+A21 reduced cell invasion by 40, 40 and 70%, compared to the positive control. The A21 derivative was more and equally effective than the AmB to inhibit cell invasion and induce apoptosis, respectively. Based on the results obtained, it can be concluded that derivative A21 has antitumor effects and produces a synergistic effect with cisplatin and carboplatin in A549 cells.