Induction of endoplasmic reticulum stress and apoptosis by a marine prostanoid in human hepatocellular carcinoma

Po Cheng Chiang, Chung Liang Chien, Shiow Lin Pan, Wen Pin Chen, Che Ming Teng, Ya Ching Shen, Jih Hwa Guh

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


Background/Aims: Hepatocellular carcinoma is a very common malignancy and is highly chemoresistant to currently available chemotherapeutic agents. We isolated a marine prostanoid, bromovulone III, from soft coral Clavularia viridis and found that it displayed effective anti-tumor activity in human hepatocellular carcinoma. The anti-tumor mechanism has been delineated in this study. Methods: Anti-tumor efficacy and apoptotic cell death were examined by sulforhodamine B and Hoechst 33342 assays. Rhodamine 123 was used to measure the change of mitochondrial membrane potential. Immunoprecipitation and Western blotting detect the involvement of several apoptosis-related proteins. Electron microscopic examination detects the morphological change of mitochondria and endoplasmic reticulum (ER). Results: Bromovulone III primarily induced mitochondria-related activation of caspase-9 and -3 in several tumor types, such as prostate cancer PC-3 and acute promyelocytic leukemia HL-60 cells. However, it primarily induced the activation of m-calpain, caspase-12, and transcription factor CHOP/GADD153 in hepatocellular carcinoma Hep3B cells, suggesting the involvement of ER stress. Furthermore, a secondary mitochondrial swelling and depolarization of mitochondrial membrane potential were subsequently triggered after ER stress, suggesting the crosstalk between ER and mitochondria. Conclusions: It is suggested that bromovulone III induces apoptosis in Hep3B cells through a mechanism that induces ER stress and leads to activation of CHOP/GADD153 and caspase-12.

Original languageEnglish
Pages (from-to)679-686
Number of pages8
JournalJournal of Hepatology
Issue number4
Publication statusPublished - Oct 2005
Externally publishedYes


  • CHOP/GADD153
  • ER stress
  • Hepatocellular carcinoma
  • Mcl-1

ASJC Scopus subject areas

  • Hepatology


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