| 18540098 |
Kawauchi K, Tobiume K, Iwashita K, Inagaki H, Morikawa T, Shibukawa Y, Moriyama Y, Hirata H, Kamata H: Cycloprodigiosin hydrochloride activates the Ras-PI3K-Akt pathway and suppresses protein synthesis inhibition-induced apoptosis in PC12 cells. Biosci Biotechnol Biochem. 2008 Jun;72(6):1564-70. Epub 2008 Jun 7.
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. |
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