Berberine Induces Autophagic Cell Death by Inactivating the Akt/mTOR Signaling Pathway.

The incidence of skin cancer has been increasing over the past decades, and melanoma is considered highly malignant because of its high rate of metastasis. Plant-derived berberine, an isoquinoline quaternary alkaloid, has been reported to possess multiple pharmacological effects against various types of cancer cells. Therefore, we treated melanoma B16F10 cells with berberine to induce cell death and understand the cell death mechanisms. The berberine-treated cells showed decreased cell viability, according to berberine concentration. However, western blot analysis of apoptosis-related marker proteins showed that the expression of Bcl-2, an apoptosis inhibitory protein, and the Bcl-2/Bax ratio were increased. Therefore, by adding 3-methyladenine to the berberine-treated cells, we investigated whether the reduced cell viability was due to autophagic cell death. The results showed that 3-methyladenine restored the cell viability decreased by berberine, suggesting autophagy. To clarify autophagic cell death, we performed transmission electron microscopy analysis, which revealed the presence of autophagosomes and autolysosomes in the cells after treatment with berberine. Next, by analyzing the expression of autophagy-related proteins, we found an increase in the levels of light chain 3A-II and Atg12-Atg5 complex in the berberine-treated cells. We then assessed the involvement of the Akt/mTOR signaling pathway and found that berberine inhibited the expression of phosphorylated Akt and mTOR. Our data demonstrated that berberine induces autophagic cell death by inactivating the Akt/mTOR signaling pathway in melanoma cells and that berberine can be used as a possible target for the development of anti-melanoma drugs.

In vitro studies on anti-obesity activity of Korean Memilmuk through AMPK activation.

The anti-obesity effect of Korean traditional food, Memilmuk, was examined through inhibition of differentiation of 3T3-L1 preadipocytes by buckwheat flour extract. Oil-Red O staining showed that lipid accumulation in adipocytes was reduced upon adding buckwheat flour extract, indicating effective inhibition of adipocyte differentiation. Buckwheat flour extract also inhibited the expression of adipogenic transcription factor, peroxisome proliferator-activated receptor γ (PPARγ), and AMP-activated protein kinase (AMPK), an intracellular regulator of energy balance. Overall, the anti-obesity effect of Korean Memilmuk might be mediated through down-regulation of PPARγ expression via AMPK activation by buckwheat flour.

[Clinical significance of bowel wall thickening detected with 64-slice multidetector computed tomography].

BACKGROUND/AIMS: The multidetector computed tomography (MDCT) scanning frequently leads to the incidental discovery of bowel wall thickening. The aim of this study was to determine the utility of gastroscopy and colonoscopy in the management of patients who had incidental discovery of bowel wall thickening on MDCT. METHODS: From May 2006 to March 2008, the abdominal MDCT reports of all patients in Chungbuk National University Hospital were reviewed. Cases with any bowel thickening were selected and then patients who received gastroscopy or colonoscopy after abdominal MDCT were re-selected. RESULTS: Gastroscopy revealed abnormal findings in 22 (95.7%) out of 23 patients, and 10 patients (43.5%) had stomach cancers. Colonoscopy revealed abnormal findings in 35 (85.4%) out of 41 patients, and 12 patients (29%) had malignant tumors. In the patients who had lymph node enlargement (p<0.001), dirty fat infiltration (p=0.025), and irregular wall thickening (p<0.001) on MDCT malignancy was observed more frequently. CONCLUSIONS: We recommend gastroscopy and colonoscopy to patients who had incidentally bowel wall thickening found on MDCT, especially those with lymph node enlargement, dirty fat infiltration, and irregular wall thickening.