• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.9
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• pp.1257-1264
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• 2016

Extracts from Artemisia annua $Linn\acute{e}$ (AAE) have various functions (anti-malaria, anti-virus, and anti-oxidant). However, the mechanism of the effects of AAE is not well known. Thus, we determined the apoptotic effects of AAE in AGS human gastric carcinoma cells. In this study, we suggested that AAE may exert cancer cell apoptosis through the Akt/mammalian target of rapamycin (mTOR)/glycogen synthase kinase (GSK)-$3{\beta}$ signal pathway and mitochondria-mediated apoptotic proteins. Activation by Akt phosphorylation resulted in cell proliferation through phosphorylation of tuberous sclerosis complex 2 (TSC2), mTOR, and GSK-$3{\beta}$. Thus, de-phosphorylation of Akt inhibited cell proliferation and induced apoptosis through inhibition of Akt, mTOR, phosphorylation of GSK-$3{\beta}$ at serine9, and control of Bcl-2 family members. Inhibition of GSK-$3{\beta}$ attenuated loss of mitochondrial membrane potential and release of cytochrome C. Bax and pro-apoptotic proteins were activated by their translocation into mitochondria from the cytosol. Translocation of Bax induced outer membrane transmission and generated apoptosis through cytochrome C release and caspase activity. We also measured 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase assay, Hoechst 33342 staining, Annexin V-PI staining, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide staining, and Western blotting. Accordingly, our study showed that AAE treatment to AGS cells resulted in inhibition of Akt, TSC2, GSK-$3{\beta}$-phosphorylated, Bim, Bcl-2, and pro-caspase 3 as well as activation of Bax and Bak expression. These results indicate that AAE induced apoptosis via a mitochondrial event through regulation of the Akt/mTOR/GSK-$3{\beta}$ signaling pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6549-6556
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• 2015

The PI3K-Akt-mTOR, $Wnt/{\beta}$-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, $Wnt/{\beta}$-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with $IC_{50}$ values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, ${\beta}$-catenin, $Gsk3{\beta}$, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, $Wnt/{\beta}$ catenin signaling pathways and induction of apoptosis pathway.