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  • Title: β-Cryptoxanthin induced anti-proliferation and apoptosis by G0/G1 arrest and AMPK signal inactivation in gastric cancer.
    Author: Gao M, Dang F, Deng C.
    Journal: Eur J Pharmacol; 2019 Sep 15; 859():172528. PubMed ID: 31288004.
    Abstract:
    β-Cryptoxanthin has been associated with reduced-risk of some cancers. However, the mechanisms of β-cryptoxanthin still remain unclearly understood in gastric cancer (GC). In this study, we examined the effect of β-cryptoxanthin on AMPK signal in human gastric cancer cells. AGS and SGC-7901 cells were treated with β-cryptoxanthin (0-40 μM) and AGS cells were injected in BALB/c (nu/nu) mice to analyze the effect of β-cryptoxanthin on GC. We found that β-cryptoxanthin induced inhibitory effect on the cell viability in a time- and concentration-dependent manner. The number of migrated cells and protein levels of matrix metalloproteinase (MMP) -2 and MMP-9 were obviously decreased. β-Cryptoxanthin treatment induced G0/G1 arrest, and reduced the expression of Cyclin E, Cyclin D1, cyclin-dependent kinases (CDK) of CDK4 and CDK6, and increased the expression of p53 and p21 in the two GC cells. Additionally, β-cryptoxanthin induced apoptosis and increased the expression of cleaved caspase-3, -8, -9 as well as cytochrome C (cyt C). β-Cryptoxanthin induced AMP-activated protein kinase (AMPK) signal inactivation by the down-regulation of protein kinase A (PKA), p-AMPK, eukaryotic elongation factor 2 kinase (eEF2k). Furthermore, β-cryptoxanthin inhibited tumor growth through suppressing the tumor volume and weight, inducing apoptotic cells. Besides, β-cryptoxanthin induced significant reductions of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). In conclusion, our data provide the novel evidence to understand the mechanism of anti-pcancer of β-cryptoxanthin and indicate that β-cryptoxanthin can serve as a promising chemopreventive agent against gastric cancer.
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