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• 1 2020-05-05T23:18:03+00:00 Avrita Brar 4 plain 2020-05-08T23:42:21+00:00

  Exploring the Effect of the Diarylpentanoid Curcumin Analog 27 in Androgen Receptor-positive Breast Cancer Cells

  Overview: We are studying the biochemical mechanisms of the androgen receptor in breast cancer cell models. 
  
  Abstract: We have previously synthesized diarylpentanoid analogs of the natural product curcumin (diferuloylmethane), one of which, ca27, has been shown to markedly down-regulate the androgen receptor (AR) in prostate cancer (PCa) cells. The AR in PCa is a major driver of uncontrolled cell proliferation and thus, a major target for therapeutic intervention in the clinical management of PCa. Therefore, ca27 has potential to foster the development of novel therapeutic organic molecules. In this work, we have begun to test ca27 in two breast cancer (BCa) cell models. MCF-7 cells express the estrogen receptor (ER), the progesterone receptor (PR), and the epidermal growth factor receptor 2 (EGFR2/Her2), while MDA-MB-231 cells do not express these receptors, which makes them of the triple-negative character. This makes them resistant against several therapies targeted to ER, PR, and EGFR2/Her2, which represents an aggressive BCa phenotype. Both cell models express the AR, which also drives cancer progression, and may be an effective target in triple-negative BCa. The effect of ca27, compared to curcumin and vehicle control, was tested using the 96-well plate based colorimetric WST assay in which 1,3,5-triphenyltetrazolium formazan is converted by mitochondrial dehydrogenases and reductases as a measure of metabolic activity and cell viability. The cells were treated with 0.1-50 micromolar ca27, curcumin, vehicle control, or nothing for 24 hours Reference absorbances at 660 nanometer were determined to account for differences in cell number between individual wells, and metabolic activity was measured over the period of four hours by determining absorbances at 440 nanometer. Reference-controlled results indicate a dose-responsive effect of ca27 and curcumin and a stronger effect of ca27 compared to curcumin. Future experimentation includes Western blot analyses to determine whether AR expression is differentially affected in the two cell models. Ca27 may be developed into an effective therapeutic modality against triple-negative BCa.
  
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