Endocrine Abstracts (2016) 42 P22 | DOI: 10.1530/endoabs.42.P22

The cellular and molecular effects of the androgen receptor agonist, Cl-4AS-1, on breast cancer cells

Mamoun Ahram, Ebtihal Mustafa, Shatha Abu Hammad, Mariam Hodhod & Malek Zihlif

Department of Physiology and Biochemistry, Faculty of Medicine, The University of Jordan, Amman, Jordan.

The notable expression of the androgen receptor (AR) in breast cancer suggests an important biological role and, hence, a window of utilizing it as a therapeutic target. Due to the undesirable side effects of AR agonists, attempts have been undertaken to develop tissue-selective androgen receptor modulators (SARMs). One such SARM is Cl-4AS-1, which has previously been shown to behave similar to the natural AR agonist, dihydrotestosterone (DHT). We aimed to examine the effects of this drug more closely at the molecular and cellular levels. Different breast cancer cell lines were utilized, namely the luminal MCF-7 cells, the molecular apocrine MDA-MB-453 cells, and the basal MDA-MB-231 cells. There was high and significant concordance in the regulation of gene expression between DHT and Cl-4AS-1. In addition, both drugs caused a similar morphological change of the MDA-MB-453 cells into a fibroblast-like phenotype. Treatment of cells with DHT resulted in increased proliferation of the MCF-7 and MDA-MB-453 cells, but not effect was observed on the growth of the MDA-MB-231 cells. On the other hand, increasing doses of Cl-4AS-1 induced an identical dose-dependent inhibition on the growth of the three cell lines. This inhibition appeared to be a result of stimulation of apoptosis. Cell cycle analysis revealed that Cl-4AS-1 blocked cell progression into the S-phase, which was followed by DNA degradation. These results indicate that Cl-4AS-1 has unique properties making it a possible drug for the treatment of breast cancer.

Presenting author: Mamoun Ahram, Department of Physiology and Biochemistry, Faculty of Medicine, The University of Jordan, Amman 11942, Jordan. Email: m.ahram@ju.edu.jo.

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