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

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1564-1570
Number of pages7
JournalBioscience, Biotechnology and Biochemistry
Volume72
Issue number6
DOIs
Publication statusPublished - 2008
Externally publishedYes

Keywords

  • Akt
  • Apoptosis
  • PC12 cells
  • Prodigiosin
  • Ras

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Cycloprodigiosin hydrochloride activates the Ras-PI3K-Akt pathway and suppresses protein synthesis inhibition-induced apoptosis in PC12 cells'. Together they form a unique fingerprint.

Cite this