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[Pt(O,O′-acac)(γ-acac)(DMS)] Induces Autophagy in Caki-1 Renal Cancer Cells

We have demonstrated the cytotoxic effects of [Pt(O,O′-acac)(γ-acac)(dimethyl sulfide (DMS))] on various immortalized cell lines, in primary cultures, and in murine xenograft models in vivo. Recently, we also showed that [Pt(O,O′-acac)(γ-acac)(DMS)] is able to kill Caki-1 renal cells both in vivo an...

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Autores principales: Antonaci, Giovanna, Cossa, Luca Giulio, Muscella, Antonella, Vetrugno, Carla, De Pascali, Sandra Angelica, Fanizzi, Francesco Paolo, Marsigliante, Santo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468382/
https://www.ncbi.nlm.nih.gov/pubmed/30845773
http://dx.doi.org/10.3390/biom9030092
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author Antonaci, Giovanna
Cossa, Luca Giulio
Muscella, Antonella
Vetrugno, Carla
De Pascali, Sandra Angelica
Fanizzi, Francesco Paolo
Marsigliante, Santo
author_facet Antonaci, Giovanna
Cossa, Luca Giulio
Muscella, Antonella
Vetrugno, Carla
De Pascali, Sandra Angelica
Fanizzi, Francesco Paolo
Marsigliante, Santo
author_sort Antonaci, Giovanna
collection PubMed
description We have demonstrated the cytotoxic effects of [Pt(O,O′-acac)(γ-acac)(dimethyl sulfide (DMS))] on various immortalized cell lines, in primary cultures, and in murine xenograft models in vivo. Recently, we also showed that [Pt(O,O′-acac)(γ-acac)(DMS)] is able to kill Caki-1 renal cells both in vivo and in vitro. In the present paper, apoptotic and autophagic effects of [Pt(O,O′-acac)(γ-acac)(DMS)] and cisplatin were studied and compared using Caki-1 cancerous renal cells. The effects of cisplatin include activation of caspases, proteolysis of enzyme poly ADP ribose polymerase (PARP), control of apoptosis modulators B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and BH3-interacting domain death agonist (Bid), and cell cycle arrest in G2/M phase. Conversely, [Pt(O,O′-acac)(γ-acac)(DMS)] did not induce caspase activation, nor chromatin condensation or DNA fragmentation. The effects of [Pt(O,O′-acac)(γ-acac)(DMS)] include microtubule-associated proteins 1A/1B light chain 3B (LC3)-I to LC3-II conversion, Beclin-1 and Atg-3, -4, and -5 increase, Bcl-2 decrease, and monodansylcadaverine accumulation in autophagic vacuoles. [Pt(O,O′-acac)(γ-acac)(DMS)] also modulated various kinases involved in intracellular transduction regulating cell fate. [Pt(O,O′-acac)(γ-acac)(DMS)] inhibited the phosphorylation of mammalian target of rapmycin (mTOR), p70S6K, and AKT, and increased the phosphorylation of c-Jun N-terminal kinase (JNK1/2), a kinase activity pattern consistent with autophagy induction. In conclusion, while in past reports the high cytotoxicity of [Pt(O,O′-acac)(γ-acac)(DMS)] was always attributed to its ability to trigger an apoptotic process, in this paper we show that Caki-1 cells die as a result of the induction of a strong autophagic process.
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spelling pubmed-64683822019-04-24 [Pt(O,O′-acac)(γ-acac)(DMS)] Induces Autophagy in Caki-1 Renal Cancer Cells Antonaci, Giovanna Cossa, Luca Giulio Muscella, Antonella Vetrugno, Carla De Pascali, Sandra Angelica Fanizzi, Francesco Paolo Marsigliante, Santo Biomolecules Article We have demonstrated the cytotoxic effects of [Pt(O,O′-acac)(γ-acac)(dimethyl sulfide (DMS))] on various immortalized cell lines, in primary cultures, and in murine xenograft models in vivo. Recently, we also showed that [Pt(O,O′-acac)(γ-acac)(DMS)] is able to kill Caki-1 renal cells both in vivo and in vitro. In the present paper, apoptotic and autophagic effects of [Pt(O,O′-acac)(γ-acac)(DMS)] and cisplatin were studied and compared using Caki-1 cancerous renal cells. The effects of cisplatin include activation of caspases, proteolysis of enzyme poly ADP ribose polymerase (PARP), control of apoptosis modulators B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and BH3-interacting domain death agonist (Bid), and cell cycle arrest in G2/M phase. Conversely, [Pt(O,O′-acac)(γ-acac)(DMS)] did not induce caspase activation, nor chromatin condensation or DNA fragmentation. The effects of [Pt(O,O′-acac)(γ-acac)(DMS)] include microtubule-associated proteins 1A/1B light chain 3B (LC3)-I to LC3-II conversion, Beclin-1 and Atg-3, -4, and -5 increase, Bcl-2 decrease, and monodansylcadaverine accumulation in autophagic vacuoles. [Pt(O,O′-acac)(γ-acac)(DMS)] also modulated various kinases involved in intracellular transduction regulating cell fate. [Pt(O,O′-acac)(γ-acac)(DMS)] inhibited the phosphorylation of mammalian target of rapmycin (mTOR), p70S6K, and AKT, and increased the phosphorylation of c-Jun N-terminal kinase (JNK1/2), a kinase activity pattern consistent with autophagy induction. In conclusion, while in past reports the high cytotoxicity of [Pt(O,O′-acac)(γ-acac)(DMS)] was always attributed to its ability to trigger an apoptotic process, in this paper we show that Caki-1 cells die as a result of the induction of a strong autophagic process. MDPI 2019-03-06 /pmc/articles/PMC6468382/ /pubmed/30845773 http://dx.doi.org/10.3390/biom9030092 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Antonaci, Giovanna
Cossa, Luca Giulio
Muscella, Antonella
Vetrugno, Carla
De Pascali, Sandra Angelica
Fanizzi, Francesco Paolo
Marsigliante, Santo
[Pt(O,O′-acac)(γ-acac)(DMS)] Induces Autophagy in Caki-1 Renal Cancer Cells
title [Pt(O,O′-acac)(γ-acac)(DMS)] Induces Autophagy in Caki-1 Renal Cancer Cells
title_full [Pt(O,O′-acac)(γ-acac)(DMS)] Induces Autophagy in Caki-1 Renal Cancer Cells
title_fullStr [Pt(O,O′-acac)(γ-acac)(DMS)] Induces Autophagy in Caki-1 Renal Cancer Cells
title_full_unstemmed [Pt(O,O′-acac)(γ-acac)(DMS)] Induces Autophagy in Caki-1 Renal Cancer Cells
title_short [Pt(O,O′-acac)(γ-acac)(DMS)] Induces Autophagy in Caki-1 Renal Cancer Cells
title_sort [pt(o,o′-acac)(γ-acac)(dms)] induces autophagy in caki-1 renal cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468382/
https://www.ncbi.nlm.nih.gov/pubmed/30845773
http://dx.doi.org/10.3390/biom9030092
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