7-Acetylsinumaximol b induces apoptosis and autophagy in human gastric carcinoma cells through mitochondria dysfunction and activation of the perk/eif2α/atf4/chop signaling pathway

Tsung Chang Tsai, Kuei Hung Lai, Jui Hsin Su, Yu Jen Wu, Jyh Horng Sheu

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

The 7-Acetylsinumaximol B (7-AB), a bioactive cembranoid, was originally discovered from aquaculture soft coral Sinularia sandensis. The current study investigated the anti-proliferative property of 7-AB towards the NCI-N87 human gastric cancer cell line. An MTT cell proliferative assay was applied to evaluate cell survival, and immunofluorescence staining and western blotting were employed to analyze the effects of 7-AB on autophagy and apoptosis. Our results showed that 7-AB exerted a concentration-dependent anti-proliferative effect on NCI-N87 cells, and fluorescence staining indicated that the effect was due to the apoptosis induced by 7-AB. In addition, the 7-AB-induced anti-proliferation towards NCI-N87 cells was associated with the release of cytochrome c from mitochondria, activation of pro-apoptotic proteins (such as caspase-3/-9, Bax and Bad), and inhibition of anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1). The 7-AB treatment also triggered endoplasmic reticulum (ER) stress, leading to activation of the PERK/elF2α/ATF4/CHOP apoptotic pathway. Furthermore, 7-AB initiated autophagy in NCI-N87 cells and induced the expression of autophagy-related proteins, including Atg3, Atg5, Atg7, Atg12, LC3-I, and LC3-II. Taken together, our findings suggested that 7-AB has the potential to be further developed as a useful anti-cancer or adjuvant agent for the treatment of human gastric cancer.

Original languageEnglish
Article number104
JournalMarine Drugs
Volume16
Issue number4
DOIs
Publication statusPublished - Apr 2018
Externally publishedYes

Keywords

  • 7-acetylsinumaximol B
  • Autophagy
  • Endoplasmic reticulum stress
  • Human gastric cancer cells
  • Mitochondrial inactivation

ASJC Scopus subject areas

  • Drug Discovery

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