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Cycloprodigiosin Hydrochloride Activates the Ras-PI3K-Akt Pathway and Suppresses Protein Synthesis Inhibition-Induced Apoptosis in PC12 Cells
- Source :
- Bioscience, Biotechnology, and Biochemistry. 72:1564-1570
- Publication Year :
- 2008
- Publisher :
- Oxford University Press (OUP), 2008.
-
Abstract
- Cycloprodigiosin hydrochloride (cPrG-HCl), a member of the prodigiosin family of compounds, has been reported to act as an H(+)/Cl(-) symporter. This compound induces apoptosis in several cancer cells and acts as an antitumor drug in animal models. In this study, we found a novel function of cPrG-HCl; to suppress cell death in PC12 cells, which is caused by protein synthesis inhibitors cycloheximide and actinomycin D. cPrG-HCl activated Akt and suppressed apoptosis, and this was accompanied by inhibition of caspase-3 activity and DNA fragmentation independently of its H(+)/Cl(-) symporter activity. Wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, and dominant-negative Ras attenuated the anti-apoptotic activity of cPrG-HCl, which indicates that cPrG-HCl activated the Ras-PI3K-Akt pathway suppressing apoptosis. On the other hand, serum-deprivation-induced apoptosis was not suppressed by cPrG-HCl.
- Subjects :
- Programmed cell death
Indoles
Apoptosis
Cycloheximide
Biology
PC12 Cells
Applied Microbiology and Biotechnology
Biochemistry
Analytical Chemistry
Wortmannin
Phosphatidylinositol 3-Kinases
chemistry.chemical_compound
Animals
Pyrroles
Molecular Biology
Protein kinase B
PI3K/AKT/mTOR pathway
Caspase 3
Organic Chemistry
General Medicine
Caspase Inhibitors
Molecular biology
Rats
Cell biology
Androstadienes
chemistry
Cytoprotection
Symporter
Dactinomycin
ras Proteins
Symporter activity
Proto-Oncogene Proteins c-akt
Signal Transduction
Biotechnology
Subjects
Details
- ISSN :
- 13476947 and 09168451
- Volume :
- 72
- Database :
- OpenAIRE
- Journal :
- Bioscience, Biotechnology, and Biochemistry
- Accession number :
- edsair.doi.dedup.....e797898e9d2a4ef19de6b577075e1d2f