IMMUNEPOTENT CRP increases intracellular calcium through ER-calcium channels, leading to ROS production and cell death in breast cancer and leukemic cell lines

Authors

  • Helen Y. Lorenzo-Anota Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, México; Tecnológico de Monterrey, The Institute for Obesity Research, Monterrey, México https://orcid.org/0000-0001-9560-4357
  • Alejandra Reyes-Ruiz Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, México https://orcid.org/0000-0001-9572-0235
  • Kenny M. Calvillo-Rodríguez Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, México https://orcid.org/0000-0001-7289-6166
  • Rodolfo Mendoza-Reveles Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, México https://orcid.org/0000-0003-1388-782X
  • Andrea P. Urdaneta-Peinado Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, México https://orcid.org/0000-0002-0782-3507
  • Karla M. Alvarez-Valadez Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, México https://orcid.org/0000-0002-6276-8010
  • Ana Carolina Martinez-Torres Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, México. E-mail: ana.martinezto@uanl.edu.mx https://orcid.org/0000-0002-6183-0089
  • Cristina Rodríguez-Padilla Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, México; LONGEVEDEN S.A. de C.V. https://orcid.org/0000-0001-5469-8449

DOI:

https://doi.org/10.17179/excli2022-5568

Keywords:

calcium, ryanodine receptor, IP3 receptor, immunotherapy, cell death, cancer

Abstract

IMMUNEPOTENT CRP (ICRP) is an immunotherapy that induces cell death in cancer cell lines. However, the molecular mechanisms of death are not completely elucidated. Here, we evaluated the implication of intracellular Ca2+ augmentation in the cell death induced by ICRP on T-ALL and breast cancer cell lines. Cell death induction and the molecular characteristics of cell death were evaluated in T-ALL and breast cancer cell lines by assessing autophagosome formation, ROS production, loss of mitochondrial membrane potential, ER stress and intracellular Ca2+ levels. We assessed the involvement of extracellular Ca2+, and the implication of the ER-receptors, IP3R and RyR, in the cell death induced by ICRP, by using an extracellular calcium chelator and pharmacological inhibitors. Our results show that ICRP increases intracellular Ca2+ levels as the first step of the cell death mechanism that provokes ROS production and loss of mitochondrial membrane potential. In addition, blocking the IP3 and ryanodine receptors inhibited ER-Ca2+ release, ROS production and ICRP-induced cell death. Taken together our results demonstrate that ICRP triggers intracellular Ca2+-increase leading to different regulated cell death modalities in T-ALL and breast cancer cell lines.

Published

2023-03-16

How to Cite

Lorenzo-Anota, H. Y., Reyes-Ruiz, A., Calvillo-Rodríguez, K. M., Mendoza-Reveles, R., Urdaneta-Peinado, A. P., Alvarez-Valadez, K. M., … Rodríguez-Padilla, C. (2023). IMMUNEPOTENT CRP increases intracellular calcium through ER-calcium channels, leading to ROS production and cell death in breast cancer and leukemic cell lines. EXCLI Journal, 22, 352–366. https://doi.org/10.17179/excli2022-5568

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