CHEMICAL AND BIOLOGICAL CHARACTERIZATION OF TRACE AMOUNT OF SEX HORMONE RECEPTOR ACTIVE COMPOUNDS IN PROSTATE CANCER-RELATED BIOLOGICAL SAMPLES

Abstract

Prostate cancer (PCa) is the most prevalent cancer in men worldwide. It is dependent on testosterone (T) and dihydrotestosterone (DHT) but estrogens play a role too. Relapses into castration resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT) are almost certain. PCa tumour consists of various cancer cells that could survive under different mechanisms after ADT. Here, attempts were made to identify the mechanisms for the individual PCa cell line using liquid chromatography tandem mass spectrometry (LC-MS/MS) and compared against results from stably-transfected cell-based reporter gene bioassays. Intracrine synthesis of potent androgens is the main reason behind CRPC. Thus, through inhibition of AKR1C3, the pivotal enzyme to synthesise T and DHT can lead to treatment of CRPC. Dimethoxycurcumin was investigated here through in vitro studies for its inhibition on AKR1C3. IC50 values of dimethoxcurcumin on AKR1C3 and AKR1C2 were obtained concurrently via LC-MS/MS measurements on T and 3a-Diol respectively.