Ilimaquinone, a marine sponge metabolite, displays anticancer activity via GADD153-mediated pathway

Pin Hsuan Lu, Shih Chieh Chueh, Fan Lu Kung, Shiow Lin Pan, Ya Ching Shen, Jih Hwa Guh

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

The marine organisms produce many metabolic substances with numerous pharmacological activities. It has been suggested that ilimaquinone, a metabolite of sea sponge, can induce vesiculation of the Golgi apparatus and display several biological activities, such as anti-human immunodeficiency virus, anti-inflammation as well as anti-microbial activities. In this study, the sulforhodamine B assays showed that ilimaquinone induced a concentration-dependent anti-proliferative effect in several types of cancer cell lines, including prostate cancer PC-3 and LNCaP, non-small cell lung cancer A549 and hepatocellular carcinoma Hep3B cells. The anticancer mechanism of ilimaquinone in the representative PC-3 cells was identified. Ilimaquinone induced a time-dependent increase of G1 phase arrest and a subsequent increase of hypodiploid sub-G1 phase (apoptosis) of the cell cycle. The arrest of the cell cycle was associated with a sustained high level of nuclear cyclin E but the absence of DNA synthesis by flow cytometric analysis, indicating an incomplete S phase. Although ilimaquinone-induced Golgi vesiculation, the data showed that the inhibition of cancer cell growth was not through the Golgi fragmentation. Several biological kinases and transcription factors were examined in this study. The data demonstrated that ilimaquinone did not activate extracellular signal-regulated kinase and phosphatidylinositol 3-kinase but induce the up-regulation and nuclear translocation of growth arrest and DNA damage inducible gene 153 (CHOP/GADD153). Furthermore, ilimaquinone-mediated anti-proliferative effect is significantly reduced in the antisense CHOP/GADD153-overexpressing cells. Ilimaquinone also inhibited DNA binding of NF-κB; however, this inhibitory effect could not explain ilimaquinone-induced anticancer effect. In summary, it is suggested that ilimaquinone induces the anti-proliferative effect through the G1 arrest of the cell cycle and the up-regulation and nuclear translocation of CHOP/GADD153.

Original languageEnglish
Pages (from-to)45-54
Number of pages10
JournalEuropean Journal of Pharmacology
Volume556
Issue number1-3
DOIs
Publication statusPublished - Feb 5 2007
Externally publishedYes

Keywords

  • Anticancer
  • CHOP/GADD153
  • G arrest
  • Ilimaquinone

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Fingerprint Dive into the research topics of 'Ilimaquinone, a marine sponge metabolite, displays anticancer activity via GADD153-mediated pathway'. Together they form a unique fingerprint.

Cite this