Sr Lee

Methyltransferase-inhibition interferes with neuronal differentiation of P19 embryonal carcinoma cells

We have analyzed the importance of substrate methylation by S-adenosylmethionine-dependent methyltransferases for neuronal differentiation of P19 embryonal carcinoma cells. We show that treatment of cells with methyltransferase inhibitor adenosine dialdehyde (AdOx) interferes with neuronal differentiation. Retinoic acid (RA) and AdOx co-treated cells had a decreased number of neurites and a flattened morphology compared with cells differentiated by RA. Also, the amount of neuronal class III tubulin (Tuj1) decreased from 76% to 9.6% with AdOx-treatment. Gene expression levels of wnt-1, brn-2, neuroD, and mash-1 were also down-regulated by AdOx-treatment. But AdOx-treatment did not up-regulate BMP-4 and GFAP genes. Treatment of RA decreased E-cadherin expression during neuronal differentiation. However, in AdOx/RA co-treated cells, E-cadherin expression was restored to the control level. Also, mRNA expression of N-cadherin decreased with AdOx-treatment. Taken together, these data show that methylation reactions might influence the cell-fate decision and neuronal differentiation of P19 cells.

Cyanidin-3-O-Sambubioside from Acanthopanax sessiliflorus Fruit Inhibits Metastasis by Downregulating MMP-9 in Breast Cancer Cells MDA-MB-231

Anthocyanins play an important role in physiological functions related to human health. This study aimed to investigate the inhibitory effect of cyanidin-3-O-sambubioside isolated from Acanthopanax sessiliflorus fruit on cancer cell metastasis. The inhibitory effect of cyanidin-3-O-sambubioside on angiogenesis was assessed by chorioallantoic membrane and tube formation assays. Cyanidin-3-O-sambubioside interrupted the formation of neovasculature and tube-like structures in a dose-dependent manner. It inhibited the wound healing migration and invasion of MDA-MB-231 cells through reconstituted extracellular matrix (Matrigel). Gelatin zymography revealed that cyanidin-3-O-sambubioside significantly decreased the secretion of matrix metalloproteinase-9 and inhibited matrix metalloproteinase-9 expression. In additional, cyanidin-3-O-sambubioside exerted an inhibitory effect on Akt phosphorylation. These results suggest that cyanidin-3-O-sambubioside inhibits metastasis processes, such as angiogenesis and invasion, in breast cancer cells through regulation of matrix metalloproteinase-9 activity.