13-Acetoxysarcocrassolide Induces Apoptosis on Human Gastric Carcinoma Cells Through Mitochondria-Related Apoptotic Pathways: p38/JNK Activation and PI3K/AKT Suppression

Autor: Yu-Jen Wu, Jeff Yi-Fu Chen, Jui‐Hsin Su, Zhong-Hao Din, Zih-Yan Yang, Yi-Jen Chen, Robert Wang, Ching-Chyuan Su
Rok vydání: 2014
Předmět:
MAP Kinase Signaling System
p38 mitogen-activated protein kinases
bcl-X Protein
Down-Regulation
Pharmaceutical Science
Biology
p38 Mitogen-Activated Protein Kinases
Article
Phosphatidylinositol 3-Kinases
p38 and JNK pathways
chemistry.chemical_compound
Stomach Neoplasms
gastric cancer cells
Annexin
Cell Line
Tumor
Drug Discovery
Humans
DAPI
Propidium iodide
lcsh:QH301-705.5
Pharmacology
Toxicology and Pharmaceutics (miscellaneous)
Protein kinase B
PI3K/AKT/mTOR pathway
bcl-2-Associated X Protein
Caspase 3
Carcinoma
apoptosis
Molecular biology
Caspase 9
Mitochondria
Up-Regulation
Cell biology
Proto-Oncogene Proteins c-bcl-2
lcsh:Biology (General)
chemistry
Apoptosis
soft coral
Cancer cell
Myeloid Cell Leukemia Sequence 1 Protein
13-acetoxysarcocrassolide
bcl-Associated Death Protein
Diterpenes
Proto-Oncogene Proteins c-akt
Signal Transduction
Zdroj: Marine Drugs
Volume 12
Issue 10
Pages 5295-5315
Marine Drugs, Vol 12, Iss 10, Pp 5295-5315 (2014)
ISSN: 1660-3397
DOI: 10.3390/md12105295
Popis: 13-acetoxysarcocrassolide (13-AC), an active compound isolated from cultured Formosa soft coral Sarcophyton crassocaule, was found to possess anti-proliferative and apoptosis-inducing activities against AGS (human gastric adenocarcinoma cells) gastric carcinoma cells. The anti-tumor effects of 13-AC were determined by MTT assay, colony formation assessment, cell wound-healing assay, TUNEL/4,6-Diamidino-2-phenylindole (DAPI) staining, Annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining and flow cytometry. 13-AC inhibited the growth and migration of gastric carcinoma cells in a dose-dependent manner and induced both early and late apoptosis as assessed by flow cytometer analysis. 13-AC-induced apoptosis was confirmed through observation of a change in ΔΨm, up-regulated expression levels of Bax and Bad proteins, down-regulated expression levels of Bcl-2, Bcl-xl and Mcl-1 proteins, and the activation of caspase-3, caspase-9, p38 and JNK. Furthermore, inhibition of p38 and JNK activity by pretreatment with SB03580 (a p38-specific inhibitor) and SP600125 (a JNK-specific inhibitor) led to rescue of the cell cytotoxicity of 13-AC-treated AGS cells, indicating that the p38 and the JNK pathways are also involved in the 13-AC-induced cell apoptosis. Together, these results suggest that 13-AC induces cell apoptosis against gastric cancer cells through triggering of the mitochondrial-dependent apoptotic pathway as well as activation of the p38 and JNK pathways.
Databáze: OpenAIRE
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