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Cycloprodigiosin Hydrochloride Activates the Ras-PI3K-Akt Pathway and Suppresses Protein Synthesis Inhibition-Induced Apoptosis in PC12 Cells

Cycloprodigiosin Hydrochloride Activates the Ras-PI3K-Akt Pathway and Suppresses Protein Synthesis Inhibition-Induced Apoptosis in PC12 Cells

Keiko Kawauchi, Kei Tobiume, Kimi Iwashita, Hiroko Inagaki, Tetsunori Morikawa, Yukinao Shibukawa, Yoshinori Moriyama, Hajime Hirata, Hideaki Kamata

Biosci Biotechnol Biochem. 2008 Jun;72(6):1564-70.

PMID: 18540098

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP56144173	Prodigiosin hydrochloride		56144-17-3	Price

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