Sarah Hester
Exploring the Effect of the Diarylpentanoid Ca27 on the Translation of the Androgen Receptor in Prostate Cancer Cells
Overview: The androgen receptor (AR) is a steroid receptor that is important in human development. In prostate cancer, the AR is often over-expressed in order to increase the survival of cancer cells. In this experiment, we treated human prostate cancer cells with the curcumin analog ca27 in order to observe the effects on the translation of AR proteins. Abstract: The androgen receptor (AR) is a steroid receptor that plays a key role in male sexual differentiation. Under normal physiological conditions, the AR acts as a ligand-mediated nuclear transcription factor that binds with androgens and is able to interact with DNA to induce the transcription of genes that can lead to proliferation or apoptosis. In prostate cancer, the AR is often over-expressed in order to increase the proliferation and survival of cancer cells. ca27, an analog of the natural product curcumin, has been shown to down-regulate AR expression in prostate cancer cells. While it has potential as a novel prostate cancer therapeutic, the exact mechanism of action of ca27 is still unknown. In this experiment we treated human LNCaP prostate cancer cells with ca27 as well as additional inhibitors of transcription, translation, and protein degradation. This allowed us to monitor the downregulation of the AR in LNCaP cells as well give an indication of at which point in protein production ca27 works to decrease AR expression (transcription, translation, or protein degradation). In conducting a Western Blot, we found the greatest downregulation of AR expression to be in cells treated with a combination of cycloheximide (a translational inhibitor) and ca27. In addition, qRT-PCR supported these findings by revealing low levels of AR mRNA in cells treated with both cycloheximide and ca27. Knowledge of the mechanism of action of ca27 will help develop further analogs of ca27 with increased AR-downregulatory capacity.
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