The downregulation of the denitrosylating enzyme S-nitrosoglutathione reductase (GSNOR, EC:1.1.1.284), is a feature of hepatocellular carcinoma (HCC). This condition causes mitochondrial rearrangements that sensitize these tumors to mitochondrial toxins, in particular to the mitochondrial complex II inhibitor alpha-tocopheryl succinate (αTOS). It has also been reported the GSNOR depletion impairs the selective degradation of mitochondria through mitophagy; however, if this contributes to GSNOR-deficient HCC cell sensitivity to αTOS and can be applied to anticancer therapies, is still not known. Here, we provide evidence that GSNOR-deficient HCC cells show defective mitophagy which contributes to αTOS toxicity. Mitophagy inhibition by Parkin (EC: 2.3.2.31) depletion enhances αTOS anticancer effects, thus suggesting that this drug could be effective in treating mitophagy-defective tumors.

Rizza, S., Di Leo, L., Mandatori, S., De Zio, D., Filomeni, G. (2020). Mitophagy contributes to alpha-tocopheryl succinate toxicity in GSNOR-deficient hepatocellular carcinoma. BIOCHEMICAL PHARMACOLOGY, 176, 113885 [10.1016/j.bcp.2020.113885].

Mitophagy contributes to alpha-tocopheryl succinate toxicity in GSNOR-deficient hepatocellular carcinoma

Rizza, Salvatore;Di Leo, Luca;De Zio, Daniela;Filomeni, Giuseppe
2020-06-01

Abstract

The downregulation of the denitrosylating enzyme S-nitrosoglutathione reductase (GSNOR, EC:1.1.1.284), is a feature of hepatocellular carcinoma (HCC). This condition causes mitochondrial rearrangements that sensitize these tumors to mitochondrial toxins, in particular to the mitochondrial complex II inhibitor alpha-tocopheryl succinate (αTOS). It has also been reported the GSNOR depletion impairs the selective degradation of mitochondria through mitophagy; however, if this contributes to GSNOR-deficient HCC cell sensitivity to αTOS and can be applied to anticancer therapies, is still not known. Here, we provide evidence that GSNOR-deficient HCC cells show defective mitophagy which contributes to αTOS toxicity. Mitophagy inhibition by Parkin (EC: 2.3.2.31) depletion enhances αTOS anticancer effects, thus suggesting that this drug could be effective in treating mitophagy-defective tumors.
giu-2020
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Alpha-tocopheryl succinate
GSNOR
Hepatocellular carcinoma
Mitophagy
S-nitrosylation
Antioxidants
Autophagosomes
Carcinoma, Hepatocellular
Cell Line, Tumor
Cell Survival
Hep G2 Cells
Liver Neoplasms
Microscopy, Confocal
Microscopy, Electron, Transmission
Mitochondria
Mitophagy
RNA Interference
alpha-Tocopherol
https://doi.org/10.1016/j.bcp.2020.113885
Rizza, S., Di Leo, L., Mandatori, S., De Zio, D., Filomeni, G. (2020). Mitophagy contributes to alpha-tocopheryl succinate toxicity in GSNOR-deficient hepatocellular carcinoma. BIOCHEMICAL PHARMACOLOGY, 176, 113885 [10.1016/j.bcp.2020.113885].
Rizza, S; Di Leo, L; Mandatori, S; De Zio, D; Filomeni, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/262402
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