Evaluación del efecto citotóxico de péptidos derivados de la secuencia LfcinB (21-25)Pal: RWOWRWQWR frente a líneas celulares humanas derivadas de cáncer de mama
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El cáncer de mama actualmente presenta la mayor incidencia y mortalidad en mujeres a nivel
mundial, los diferentes tratamientos para esta enfermedad son altamente invasivos afectando
tanto la calidad de vida como la autoestima de los pacientes. Es por esto, que se requieren
nuevos abordajes terapéuticos con mayor selectividad que no induzcan resistencia ni generen
efectos adversos. Dentro de este contexto surgen los péptidos antimicrobianos (AMPs) los
cuales han presentado efecto citotóxico contra células cancerosas; el péptido palindrómico
derivado de lactoferricina bovina LfcinB (21-25hat: 1 RWQWRWQWR9 ha presentado actividad
anticancerígena contra líneas celulares humanas derivadas de cáncer oral y de mama. En este
trabajo se evaluó el efecto citotóxico de péptidos análogos de la secuencia palindrómica (sean
de Alaninas) frente a líneas derivadas de cáncer de mama MDA-MB-468, MDA-MB-231, MCF-
7 y cultivo primario de fibroblastos, determinando que el efecto citotóxico se ve disminuido por
la modificación de cualquiera de los residuos de la secuencia. El péptido palindrómico generó
efecto citotóxico selectivo sobre las líneas celulares evaluadas con cambios morfológicos
característicos de apoptosis. Además, se evaluó de manera preliminar el tipo de muerte celular
generada por este péptido contra la línea celular MCF-7 mediante citometría de flujo y cambio
en la expresión génica relativa , permitiéndonos determinar que su efecto está mediado
mayoritariamente por procesos apoptóticos. Este trabajo permitió identificar un péptido
citotóxico y selectivo contra líneas celulares derivadas de cáncer de mamá, cuya secuencia
puede ser considerada promisoria para el desarrollo de agentes terapéuticos.
Breast cancer currently has the highest incidence and mortality in women worldwide, the different treatments for this disease are highly invasive affecting both the quality of life and the self-esteem of patients. That is why new therapeutic approaches with greater selectivity which do not induce resistance or generate adverse effects are required. Within this context, antimicrobial peptides (AMPs) arise which have had a cytotoxic effect against cancer cells; palindromic peptide derived from bovine lactoferricin LfcinB (21-25hat: 1RWQWRWQWR9 has presented anticancer activity against human celllines derived from oral and breast cancer. In this work, the cytotoxic effect of peptide analogs of the palindromic sequence (Alanine sean) was evaluated against lines derived from breast cancer MDA-MB-468, MDA-MB-231, MCF-7 and primary fibroblast culture, determining that the cytotoxic effect is diminished by the modification of any of the sequence residues. The palindromic peptide generated a selective cytotoxic effect on celllines evaluated with morphological changes characteristic of apoptosis. In addition, the mechanism of action of this peptide against the MCF-7 cellline was evaluated preliminary by flow cytometry and change in relative gene expression, supporting us to determine that its effect is mediated by apoptotic processes. This work allowed to identify a cytotoxic and selective peptide against celllines derived from breast cancer, whose sequence can be considered promising for the development of therapeutic agents.
Breast cancer currently has the highest incidence and mortality in women worldwide, the different treatments for this disease are highly invasive affecting both the quality of life and the self-esteem of patients. That is why new therapeutic approaches with greater selectivity which do not induce resistance or generate adverse effects are required. Within this context, antimicrobial peptides (AMPs) arise which have had a cytotoxic effect against cancer cells; palindromic peptide derived from bovine lactoferricin LfcinB (21-25hat: 1RWQWRWQWR9 has presented anticancer activity against human celllines derived from oral and breast cancer. In this work, the cytotoxic effect of peptide analogs of the palindromic sequence (Alanine sean) was evaluated against lines derived from breast cancer MDA-MB-468, MDA-MB-231, MCF-7 and primary fibroblast culture, determining that the cytotoxic effect is diminished by the modification of any of the sequence residues. The palindromic peptide generated a selective cytotoxic effect on celllines evaluated with morphological changes characteristic of apoptosis. In addition, the mechanism of action of this peptide against the MCF-7 cellline was evaluated preliminary by flow cytometry and change in relative gene expression, supporting us to determine that its effect is mediated by apoptotic processes. This work allowed to identify a cytotoxic and selective peptide against celllines derived from breast cancer, whose sequence can be considered promising for the development of therapeutic agents.