Acid ceramidase controls apoptosis and increases autophagy in human melanoma cells treated with doxorubicin

Abstract Acid ceramidase (AC) is a lysosomal hydrolase encoded by the ASAH1 gene, which cleaves ceramides into sphingosine and fatty acid. AC is expressed at high levels in most human melanoma cell lines and may confer resistance against chemotherapeutic agents. One such agent, doxorubicin, was show...

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Autores principales:	Michele Lai, Rachele Amato, Veronica La Rocca, Mesut Bilgin, Giulia Freer, Piergiorgio Spezia, Paola Quaranta, Daniele Piomelli, Mauro Pistello
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bb95459d959446d39674ef812a131ef5
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spelling	oai:doaj.org-article:bb95459d959446d39674ef812a131ef52021-12-02T15:00:39ZAcid ceramidase controls apoptosis and increases autophagy in human melanoma cells treated with doxorubicin10.1038/s41598-021-90219-12045-2322https://doaj.org/article/bb95459d959446d39674ef812a131ef52021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90219-1https://doaj.org/toc/2045-2322Abstract Acid ceramidase (AC) is a lysosomal hydrolase encoded by the ASAH1 gene, which cleaves ceramides into sphingosine and fatty acid. AC is expressed at high levels in most human melanoma cell lines and may confer resistance against chemotherapeutic agents. One such agent, doxorubicin, was shown to increase ceramide levels in melanoma cells. Ceramides contribute to the regulation of autophagy and apoptosis. Here we investigated the impact of AC ablation via CRISPR-Cas9 gene editing on the response of A375 melanoma cells to doxorubicin. We found that doxorubicin activates the autophagic response in wild-type A375 cells, which effectively resist apoptotic cell death. In striking contrast, doxorubicin fails to stimulate autophagy in A375 AC-null cells, which rapidly undergo apoptosis when exposed to the drug. The present work highlights changes that affect melanoma cells during incubation with doxorubicin, in A375 melanoma cells lacking AC. We found that the remarkable reduction in recovery rate after doxorubicin treatment is strictly associated with the impairment of autophagy, that forces the AC-inhibited cells into apoptotic path.Michele LaiRachele AmatoVeronica La RoccaMesut BilginGiulia FreerPiergiorgio SpeziaPaola QuarantaDaniele PiomelliMauro PistelloNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michele Lai Rachele Amato Veronica La Rocca Mesut Bilgin Giulia Freer Piergiorgio Spezia Paola Quaranta Daniele Piomelli Mauro Pistello Acid ceramidase controls apoptosis and increases autophagy in human melanoma cells treated with doxorubicin
description	Abstract Acid ceramidase (AC) is a lysosomal hydrolase encoded by the ASAH1 gene, which cleaves ceramides into sphingosine and fatty acid. AC is expressed at high levels in most human melanoma cell lines and may confer resistance against chemotherapeutic agents. One such agent, doxorubicin, was shown to increase ceramide levels in melanoma cells. Ceramides contribute to the regulation of autophagy and apoptosis. Here we investigated the impact of AC ablation via CRISPR-Cas9 gene editing on the response of A375 melanoma cells to doxorubicin. We found that doxorubicin activates the autophagic response in wild-type A375 cells, which effectively resist apoptotic cell death. In striking contrast, doxorubicin fails to stimulate autophagy in A375 AC-null cells, which rapidly undergo apoptosis when exposed to the drug. The present work highlights changes that affect melanoma cells during incubation with doxorubicin, in A375 melanoma cells lacking AC. We found that the remarkable reduction in recovery rate after doxorubicin treatment is strictly associated with the impairment of autophagy, that forces the AC-inhibited cells into apoptotic path.
format	article
author	Michele Lai Rachele Amato Veronica La Rocca Mesut Bilgin Giulia Freer Piergiorgio Spezia Paola Quaranta Daniele Piomelli Mauro Pistello
author_facet	Michele Lai Rachele Amato Veronica La Rocca Mesut Bilgin Giulia Freer Piergiorgio Spezia Paola Quaranta Daniele Piomelli Mauro Pistello
author_sort	Michele Lai
title	Acid ceramidase controls apoptosis and increases autophagy in human melanoma cells treated with doxorubicin
title_short	Acid ceramidase controls apoptosis and increases autophagy in human melanoma cells treated with doxorubicin
title_full	Acid ceramidase controls apoptosis and increases autophagy in human melanoma cells treated with doxorubicin
title_fullStr	Acid ceramidase controls apoptosis and increases autophagy in human melanoma cells treated with doxorubicin
title_full_unstemmed	Acid ceramidase controls apoptosis and increases autophagy in human melanoma cells treated with doxorubicin
title_sort	acid ceramidase controls apoptosis and increases autophagy in human melanoma cells treated with doxorubicin
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bb95459d959446d39674ef812a131ef5
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Acid ceramidase controls apoptosis and increases autophagy in human melanoma cells treated with doxorubicin

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