Abstract
The mortality of gastric cancer (GC) is increasing due to its high rates of recurrence and metastasis. Zeylenone (Zey), a type of naturally occurring cyclohexene oxide, was demonstrated to be effective in cancer patients. The aim of this study is to explore the anti-cancer effect of Zey against gastric cancer both in vitro and in vivo, as well as the underlying mechanisms. We found that Zey inhibited gastric tumor growth, as demonstrated by in vitro gastric cancer cell lines and in a human gastric cancer xenograft mouse model. Furthermore, Zey induced substantial apoptosis through a mitochondrial apoptotic pathway, involving mitochondrial transmembrane potential loss, caspase-3 activation, anti-apoptotic protein downregulation, and pro-apoptotic protein upregulation. Notably, we revealed for the first time that Zey suppressed invasion and migration by wound healing and transwell chamber assays. Through Western blotting, we further explored the potential mechanism of Zey’s anti-cancer activity. We found that Zey downregulated the expression of matrix metalloproteinase 2/9 (MMP 2/9) and inhibited the phosphorylation of AKT and ERK. In short, Zey, which induced mitochondrial apoptosis and inhibited proliferation, migration, and invasion, may be developed as a novel drug for the treatment of gastric cancer.
Highlights
Gastric cancer (GC) represents a health threat as the fourth most common cancer and the second leading cause of cancer death worldwide [1,2]
We found that Zey inhibited gastric tumor growth, as demonstrated by in in vitro gastric cancer cell lines and in a human gastric cancer xenograft mouse model
We found that Zey suppressed the metastasis of gastric metastasis gastric cancer cellslevels by decreasing protein levels ofand
Summary
Gastric cancer (GC) represents a health threat as the fourth most common cancer and the second leading cause of cancer death worldwide [1,2]. Studies showed that more than 950,000 new diagnoses are made every year, and an estimated 720,000 patients died from gastric cancer in 2012 [3]. Even with the rapid improvement of healthcare and detection [4], gastric cancer is still a nightmare, and the relative five-year survival rates for GC are only about 20% in most areas of the world [5]. The burden of gastric cancer remains high, especially in Asia, Latin America, and central and eastern Europe [6]. Gastric cancer is characterized by uncontrolled cell proliferation and metastasis [2]. Research into the field of metastasis, compared with other key events such as proliferation, is lacking. Identifying new drugs with anti-metastasis and anti-proliferation characteristics is the focus in GC treatment
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