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Mitophagy contributes to alpha-tocopheryl succinate toxicity in GSNOR-deficient hepatocellular carcinoma.
- Source :
-
Biochemical Pharmacology . Jun2020, Vol. 176, pN.PAG-N.PAG. 1p. - Publication Year :
- 2020
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HEPATOCELLULAR carcinoma
*SUCCINATES
*ANAPLASTIC lymphoma kinase
*TOXINS
Subjects
Details
- Language :
- English
- ISSN :
- 00062952
- Volume :
- 176
- Database :
- Academic Search Index
- Journal :
- Biochemical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 143460432
- Full Text :
- https://doi.org/10.1016/j.bcp.2020.113885