Contribution of endoplasmic reticulum stress, MAPK and PI3K/Akt pathways to the apoptotic death induced by a penicillin derivative in melanoma cells

Abstract: We have previously examined the in vitro and in vivo antitumor action of TAP7f, a synthetic triazolylpeptidyl penicillin, on murine melanoma cells. In this work, we explored the signal transduction pathways modulated by TAP7f in murine B16- F0 and human A375 melanoma cells, and the contr...

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Autores principales: Bellizzi, Yanina, Anselmi Relats, Juan Manuel, Cornier, Patricia G., Delpiccolo, Carina M. L., Mata, Ernesto G., Cayrol, María Florencia, Cremaschi, Graciela A., Blank, Viviana C., Roguin, Leonor P.
Formato: Artículo
Lenguaje:Inglés
Publicado: Springer 2022
Materias:
APOPTOSIS
CELULAS
MELANOMA
PENICILINA TRIAZOLIL PEPTIDIL ANTITUMORAL
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/15398
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-15398
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic APOPTOSIS
CELULAS
MELANOMA
PENICILINA TRIAZOLIL PEPTIDIL ANTITUMORAL
spellingShingle APOPTOSIS
CELULAS
MELANOMA
PENICILINA TRIAZOLIL PEPTIDIL ANTITUMORAL
Bellizzi, Yanina
Anselmi Relats, Juan Manuel
Cornier, Patricia G.
Delpiccolo, Carina M. L.
Mata, Ernesto G.
Cayrol, María Florencia
Cremaschi, Graciela A.
Blank, Viviana C.
Roguin, Leonor P.
Contribution of endoplasmic reticulum stress, MAPK and PI3K/Akt pathways to the apoptotic death induced by a penicillin derivative in melanoma cells
topic_facet APOPTOSIS
CELULAS
MELANOMA
PENICILINA TRIAZOLIL PEPTIDIL ANTITUMORAL
description Abstract: We have previously examined the in vitro and in vivo antitumor action of TAP7f, a synthetic triazolylpeptidyl penicillin, on murine melanoma cells. In this work, we explored the signal transduction pathways modulated by TAP7f in murine B16- F0 and human A375 melanoma cells, and the contribution of some intracellular signals to the apoptotic cell death. TAP7f decreased ERK1/2 phosphorylation and increased phospho-p38, phospho-JNK and phospho-Akt levels. ERK1/2 blockage suppressed cell growth, while inhibition of p38, JNK and PI3K-I pathways reduced the antitumor effect of TAP7f. Pharmacological inhibition of p38 and JNK, or blockage of PI3K-I/Akt cascade with a dominant negative PI3K-I mutant diminished Bax expression levels and PARP-1 cleavage, indicating the involvement of these pathways in apoptosis. PI3K-I/Akt inhibition also favored an autophagic response, as evidenced by the higher expression levels of Beclin-1 and LC3-II detected in transfected cells exposed to TAP7f. However, although PI3K-I/Akt blockage promoted an autophagic survival response, this mechanism appears not to be critical for TAP7f antitumor action. It was also shown that TAP7f induced ER stress by enhancing the expression of ER stress-related genes and proteins. Downregulation of CHOP protein with specific siRNA increased cell growth and decreased cleavage of PARP-1, supporting its role in apoptosis. Furthermore, it was found that activation of p38, JNK and Akt occurred downstream ER perturbation. In summary, our results showed that TAP7f triggers an apoptotic cell death in melanoma cells through induction of ER stress and activation of p38, JNK and PI3K-I/Akt pathways.
format Artículo
author Bellizzi, Yanina
Anselmi Relats, Juan Manuel
Cornier, Patricia G.
Delpiccolo, Carina M. L.
Mata, Ernesto G.
Cayrol, María Florencia
Cremaschi, Graciela A.
Blank, Viviana C.
Roguin, Leonor P.
author_facet Bellizzi, Yanina
Anselmi Relats, Juan Manuel
Cornier, Patricia G.
Delpiccolo, Carina M. L.
Mata, Ernesto G.
Cayrol, María Florencia
Cremaschi, Graciela A.
Blank, Viviana C.
Roguin, Leonor P.
author_sort Bellizzi, Yanina
title Contribution of endoplasmic reticulum stress, MAPK and PI3K/Akt pathways to the apoptotic death induced by a penicillin derivative in melanoma cells
title_short Contribution of endoplasmic reticulum stress, MAPK and PI3K/Akt pathways to the apoptotic death induced by a penicillin derivative in melanoma cells
title_full Contribution of endoplasmic reticulum stress, MAPK and PI3K/Akt pathways to the apoptotic death induced by a penicillin derivative in melanoma cells
title_fullStr Contribution of endoplasmic reticulum stress, MAPK and PI3K/Akt pathways to the apoptotic death induced by a penicillin derivative in melanoma cells
title_full_unstemmed Contribution of endoplasmic reticulum stress, MAPK and PI3K/Akt pathways to the apoptotic death induced by a penicillin derivative in melanoma cells
title_sort contribution of endoplasmic reticulum stress, mapk and pi3k/akt pathways to the apoptotic death induced by a penicillin derivative in melanoma cells
publisher Springer
publishDate 2022
url https://repositorio.uca.edu.ar/handle/123456789/15398
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