Cell-Permeable Bak BH3 Peptide Induces Chemosensitization of Hematologic Malignant Cells.

Autor: Ugarte-Alvarez O; Unit of Investigative Research on Oncological Diseases, Children's Hospital of Mexico Federico Gomez, Mexico City 06720, Mexico., Muñoz-López P; Unit of Investigative Research on Oncological Diseases, Children's Hospital of Mexico Federico Gomez, Mexico City 06720, Mexico.; Posgrado en Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico., Moreno-Vargas LM; Research Unit on Computational Biology and Drug Design, Children's Hospital of Mexico Federico Gomez, Mexico City 06720, Mexico., Prada-Gracia D; Research Unit on Computational Biology and Drug Design, Children's Hospital of Mexico Federico Gomez, Mexico City 06720, Mexico., Mateos-Chávez AA; Unit of Investigative Research on Oncological Diseases, Children's Hospital of Mexico Federico Gomez, Mexico City 06720, Mexico., Becerra-Báez EI; Unit of Investigative Research on Oncological Diseases, Children's Hospital of Mexico Federico Gomez, Mexico City 06720, Mexico.; Posgrado en Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico., Luria-Pérez R; Unit of Investigative Research on Oncological Diseases, Children's Hospital of Mexico Federico Gomez, Mexico City 06720, Mexico.
Jazyk: angličtina
Zdroj: Journal of oncology [J Oncol] 2020 Nov 30; Vol. 2020, pp. 2679046. Date of Electronic Publication: 2020 Nov 30 (Print Publication: 2020).
DOI: 10.1155/2020/2679046
Abstrakt: Hematologic malignancies such as leukemias and lymphomas are among the leading causes of pediatric cancer death worldwide, and although survival rates have improved with conventional treatments, the development of drug-resistant cancer cells may lead to patient relapse and limited possibilities of a cure. Drug-resistant cancer cells in these hematologic neoplasms are induced by overexpression of the antiapoptotic B-cell lymphoma 2 (Bcl-2) protein families, such as Bcl- XL , Bcl-2, and Mcl-1. We have previously shown that peptides from the BH3 domain of the proapoptotic Bax protein that also belongs to the Bcl-2 family may antagonize the antiapoptotic activity of the Bcl-2 family proteins, restore apoptosis, and induce chemosensitization of tumor cells. Furthermore, cell-permeable Bax BH3 peptides also elicit antitumor activity and extend survival in a murine xenograft model of human B non-Hodgkin's lymphoma. However, the activity of the BH3 peptides of the proapoptotic Bak protein of the Bcl-2 family against these hematologic malignant cells requires further characterization. In this study, we report the ability of the cell-permeable Bak BH3 peptide to restore apoptosis and induce chemosensitization of acute lymphoblastic leukemia and non-Hodgkin's lymphoma cell lines, and this event is enhanced with the coadministration of cell-permeable Bax BH3 peptide and represents an attractive approach to improve the patient outcomes with relapsed or refractory hematological malignant cells.
Competing Interests: The authors declare that they have no conflicts of interest.
(Copyright © 2020 Omar Ugarte-Alvarez et al.)
Databáze: MEDLINE
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