Publication Date

Spring 2016

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Advisor

Brandon White

Keywords

Cyclin B1, cyclins, Dietary compounds, polyphenols, triple negative breast cancer, Walnut

Subject Areas

Molecular biology

Abstract

Walnuts are rich in polyphenols and have potential for cancer prevention and treatment. Our lab has previously shown that a walnut extract (WE) is able to block the cell cycle at the S and G2 phases of cell division with a corresponding decrease in the amount of the cyclin B1 protein and induce cell death in human breast cancer cells (Le et al., 2014). The aim of the current research was to identify whether this effect on the expression of cyclin B1 was at the transcriptional or the translational level. A cycloheximide (CHX) chase revealed that a WE does not affect the half-life of cyclin B1. A time course analysis in conjunction with real-time quantitative polymerase chain reaction (RT-qPCR) revealed that a WE decreased the number of cyclin B1 transcripts. A similar effect was observed with other cyclins, cell proliferation marker Ki67, and the transcription factor Sp1. These results suggested that WE affect the expression of cyclins and genes involved in cell proliferation. Further, there was no significant decrease in the levels of mRNA of Notch1, RelA/p65, and MXD4. We also confirmed that repression of the cyclin B1 gene was dose dependent and was specific to the ellagitannins, tellimagrandin I and casuarictin, isolated from walnuts. Quercetin, a flavanol also found in walnuts, did not have any effect on cyclin B1 expression. Overall, our results suggest that in WE-treated MDA-MB-231, a decrease in the amount of the cyclin B1 protein is correlated with a corresponding decrease in its transcription

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