The Inhibition of Human Epithelial Cells Proliferation by Oridoninthrough Interrupted Notch Signalling Pathway

Abstract

Since the Notch signaling pathway plays a vital role in cell proliferation, oridonin restrains cancer cell growth bylimiting the Notch pathway. The study aims to investigate whether oridonin can kill normal epithelial cells similar tocancer cells in vitro. Also, the study aims to find whether the inhibition of Notch-1 by oridonin is on a transcriptionallevel. Methods: The study will use human epithelial cells (MCF10A) and breast cancer cells (MCF7). These two typesof cells will be treated with various concentrations of oridonin (0.01mM, 0.1mM, 1mM, and 10mM) for a differentamount of time (24h, 48h, 72h). The cell viability will be measured by WST-1 assay. Possible Results: There areeight possible results, three for the proliferation of epithelial cells and two for the transcriptional level of Notch-1 inepithelial cells. Normal epithelial cells experience a more significant loss of viable cells compared with cancer cells:(1) with decreased transcription and expression of Notch-1; (2) with decreased expression of Notch-1 but no decreasein transcription; (3) with a decrease in transcription but no decrease in expression of Notch-1 (4) with no decreasein expression and transcription of Notch-1. Normal epithelial cells experience a similar or less loss of viable cellscompared with cancer cells, (5) with decreased transcription and expression of Notch-1; (6) with decreased expressionof Notch-1 but no decrease in transcription; (7) with a decrease in transcription but no decrease in expression of Notch-1(8) with no decrease in expression and transcription of Notch-1. Conclusion: The loss of normal cells is considered atrade-off for the anti-tumor activity of oridonin. If little or no damage to non-tumorigenic epithelial cells is detected,then oridonin may be a good cure for breast cancer with fewer side effects. Also, by investigating whether the inhibitionof Notch-1 by oridonin is on a transcriptional level, we can gain more insights into the mechanism of inhibition.