Abstract
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.
Highlights
Gastric cancer (GC), a gastrointestinal cancer, is ranked as the second most common cause of cancer-related death in the world [1,2]
These results demonstrated that treatment with 13-AC significantly induced early apoptosis of AGS cells, and this apoptotic effect was exerted in a dose-dependent manner
In this study, increased expression levels of Bax and cytochrome C were detected in the 13-AC-treated cells, implying that the 13-AC-induced apoptosis was associated with activation of the mitochondrial-related pathway in AGS cells
Summary
Gastric cancer (GC), a gastrointestinal cancer, is ranked as the second most common cause of cancer-related death in the world [1,2]. Many studies have revealed that the high mortality rate of gastric cancer is related to the lack of an effective therapy for advanced stages of the disease. The high mortality rate emphasizes the need for effective medical treatments for patients with advanced stages of gastric cancer [8]. The initiation of intrinsic pathways is caused by the stimulation of biochemical events, resulting in the organelles inside the cells experiencing enhanced intracellular stresses In this pathway, mitochondria and the endoplasmic reticulum (ER). The results showed that apoptosis was induced by 13-AC through the mitochondrial-dependent apoptotic pathway with p38 and JNK activation These results provide useful information regarding the biochemical aspects of the cytotoxic effects of 13-AC on AGS cells and will accelerate drug development and improve the monitoring of human gastric carcinoma
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
