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• 1 2020-05-06T00:11:41+00:00 Emma Beale 5 plain 2020-05-08T23:40:56+00:00

  
  Exploring the Effect of the Diarylpentanoid Ca27 on the Degradation of the Androgen Receptor in Prostate Cancer Cells

  Overview: This study addresses a possible mechanism of action for the molecule ca27, which is known to decrease the protein AR in prostate cancer cells. AR helps cells grow and when uncontrolled can lead to cancer; ca27 causes cancer cell death by combating expression of AR. Understanding how ca27 downregulates AR lends insight into therapeutic treatments.
  
  Abstract: The present study addresses a possible mechanism of action for the diarylpentanoid curcumin analog 27 (ca27), which has been shown to downregulate the androgen receptor (AR) in prostate cancer (PCa) cells. Prostate cells, both normal and cancerous, express the AR, which functions as a hormone-induced cytoplasmic/nuclear receptor and transcription factor promoting cell growth and survival. In PCa, AR expression and activity are overexpressed, and the AR is a major oncoprotein leading to uncontrolled cell growth. ca27 is a synthetic diarylpentanoid analog of the natural product curcumin. Previous research in Dr. Bisoffi’s lab has shown that ca27 downregulates AR expression at low micromolar concentrations in prostate cancer cells. However, the mechanism of action is unknown. The goal of the present work is to determine at what step of the central biological dogma ca27 acts to downregulate AR expression. Specifically, we hypothesize that ca27 interferes with AR protein stability by enhancing its degradation. Using specific inhibitors of transcription, translation, and degradation, applied to human androgen-dependent LNCaP prostate adenocarcinoma cells, preliminary data is presented based on the method of sodium dodecyl sulfate gel electrophoresis (SDS-PAGE) followed by immunological detection by Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Our preliminary data indicates that ca27 is a mediator of protein degradation. A better understanding of the mechanism of action of ca27 with respect to its activity to downregulate AR expression will build the foundation for the development of organic small molecules as therapeutic candidates in the clinical management of PCa.
  
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