Abstract
Sinularin is an active compound isolated from the cultured soft coral Sinularia flexibilis. In this study, we investigated the effects of sinularin on two human gastric cancer cell lines, AGS and NCI-N87. Our results demonstrated that sinularin suppressed the proliferation of gastric cancer cells in a dose-dependent manner and induced apoptosis. In addition, the loss of mitochondrial membrane potential, the release of cytochrome C, the activation of Bax, Bad and caspase-3/9, and the suppression of p-Bad, Bcl-xL and Bcl-2 were observed in the cells treated with sinularin. This finding suggests that sinularin-induced apoptosis is associated with mitochondria-mediated apoptosis and occurs through caspase-dependent pathways. Furthermore, sinularin inhibited the phosphoinositol 3-kinase/Akt/mechanistic target of the rapamycin signaling pathway. Taken together, our results show that sinularin-induced apoptosis is mediated by activation of the caspase cascade and mitochondrial dysfunction. Our findings suggest that sinularin merits further evaluation as a chemotherapeutic agent for human gastric cancer.
Highlights
According to a recent report from the World Health Organization (WHO), gastric cancer is the fifth most common cancer worldwide and was the third leading cause of cancer death [1]
Sinularin possessed antiproliferative and apoptosis-inducing activities against AGS and NCI-N87 cells. These results showed that sinularin inhibits cell proliferation and induces apoptosis through mitochondria-dependent apoptosis and inhibition of the Phosphoinositol 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway
An MTT assay was used to evaluate the cytotoxic effect of sinularin on AGS and NCI-N87 gastric cancer cell lines
Summary
According to a recent report from the World Health Organization (WHO), gastric cancer is the fifth most common cancer worldwide and was the third leading cause of cancer death [1]. Evidence from epidemiological studies has shown that Helicobacter pylori infection is the main cause of gastric cancer [1]. Because its symptoms are often nonspecific, diagnosis is often delayed until metastasis occurs. Phosphoinositol 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling is a crucial pathway involved in cell survival and differentiation, proliferation, apoptosis and metastasis [3,4]. Active Akt binds to the related G protein-coupled receptors or receptor tyrosine kinase of growth factors such as epidermal growth factor and insulin-like growth factor, generating phosphatidylinositol triphosphate (PIP3) at the plasma membrane. Activation of PI3K occurs when PI3K is recruited to the phosphotyrosine residues of its ligand through its Src
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