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Inhibition of acid ceramidase elicits mitochondrial dysfunction and oxidative stress in pancreatic cancer cells
- Source :
- Cancer Science
- Publication Year :
- 2021
- Publisher :
- John Wiley and Sons Inc., 2021.
-
Abstract
- Although the inhibition of acid ceramidase (AC) is known to induce antitumor effects in various cancers, there are few reports in pancreatic cancer, and the underlying mechanisms remain unclear. Moreover, there is currently no safe administration method of AC inhibitor. Here the effects of gene therapy using siRNA and shRNA for AC inhibition with its mechanisms for pancreatic cancer were investigated. The inhibition of AC by siRNA and shRNA using an adeno‐associated virus 8 (AAV8) vector had antiproliferative effects by inducing apoptosis in pancreatic cancer cells and xenograft mouse model. Acid ceramidase inhibition elicits mitochondrial dysfunction, reactive oxygen species accumulation, and manganese superoxide dismutase suppression, resulting in apoptosis of pancreatic cancer cells accompanied by ceramide accumulation. These results elucidated the mechanisms underlying the antitumor effect of AC inhibition in pancreatic cancer cells and suggest the potential of the AAV8 vector to inhibit AC as a therapeutic strategy.<br />Acid ceramidase inhibition elicits mitochondrial dysfunction, reactive oxygen species accumulation, and manganese superoxide dismutase suppression, resulting in apoptosis of pancreatic cancer cells accompanied by ceramide accumulation. The current study elucidated the mechanisms underlying the antitumor effect of AC inhibition in pancreatic cancer cells and suggest the potential of the AAV8 vector to inhibit AC as a therapeutic strategy.
- Subjects :
- Male
Cancer Research
Ceramide
Mitochondrial Diseases
Acid Ceramidase
Genetic enhancement
Genetic Vectors
pancreatic ductal adenocarcinoma
Mice, Nude
Apoptosis
medicine.disease_cause
Ceramides
Small hairpin RNA
chemistry.chemical_compound
Mice
Random Allocation
Cell, Molecular, and Stem Cell Biology
Pancreatic cancer
Cell Line, Tumor
mitochondrial dysfunction
medicine
oxidative stress
Animals
Humans
RNA, Small Interfering
chemistry.chemical_classification
Reactive oxygen species
Mice, Inbred BALB C
Superoxide Dismutase
adeno‐associated virus
General Medicine
Original Articles
Genetic Therapy
Dependovirus
medicine.disease
Xenograft Model Antitumor Assays
Pancreatic Neoplasms
Oncology
chemistry
Cancer research
Original Article
Reactive Oxygen Species
Oxidative stress
Subjects
Details
- Language :
- English
- ISSN :
- 13497006 and 13479032
- Volume :
- 112
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Cancer Science
- Accession number :
- edsair.doi.dedup.....d6e207306dc392483093658074aeabfa