Osajin displays potential antiprostate cancer efficacy via impairment of fatty acid synthase and androgen receptor expression

• Published in: The Prostate 2019-09, Vol.79 (13), p.1543-1552
• Main Authors: Huang, Shih‐Yin, Huang, Guan‐Jhong, Hsieh, Po‐Fan, Wu, Hsi‐Chin, Huang, Wen‐Chin
• Format: Article
• Language: English
• Subjects: androgen receptor; Androgen receptors; Androgens; Annexin V; antiprostate cancer efficacy; Apoptosis; Apoptosis - drug effects; Caspase; Castration; Cell Growth Processes - drug effects; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Down-Regulation - drug effects; Enzymatic activity; Fatty Acid Synthase, Type I - antagonists & inhibitors; Fatty Acid Synthase, Type I - metabolism; fatty acid/lipid biosynthesis; Fatty acids; Fatty-acid synthase; Fluorescein isothiocyanate; Humans; Isoflavones - pharmacology; Kallikreins - metabolism; Lipogenesis; Lipogenesis - drug effects; Male; Neoplasm Invasiveness; osajin; Propidium iodide; Prostate; Prostate-Specific Antigen - metabolism; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - metabolism; Prostatic Neoplasms, Castration-Resistant - pathology; Receptors, Androgen - biosynthesis; Wound healing
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.23876

Background Currently, antiprostate cancer (PCa) drugs, including androgen deprivation therapy (ADT), are initially effective; however, most patients with PCa who receive ADT eventually progress to deadly aggressiveness. There is an urgent need to seek alternative strategies to cure this lethal disease. Activation of lipogenesis has been demonstrated to lead to PCa progression. Therefore, targeting the aberrant lipogenic activity could be developed therapeutically in PCa. The aim of this study is to investigate the molecular basis and efficacy of osajin, a bioactive prenylated isoflavonoid, in PCa. Methods PCa cells, LNCaP (androgen‐sensitive) and C4‐2 (androgen‐insensitive/castration‐resistant), were used in this study. Proliferation, migration, and invasion analyses were conducted by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) method, a wound healing assay, and the transwell method. Lipogenesis was determined by a Fatty Acid Quantification Kit and oil red O staining. Apoptosis was assessed by annexin V‐fluorescein isothiocyanate/propidium iodide staining, caspase enzymatic activity, and Western blot analyses. Results Osajin inhibited fatty acid synthase (FASN) expression, a key enzyme for lipogenesis, in PCa cells. By inhibiting FASN, osajin decreased the fatty‐acid levels and lipid accumulation. Significantly, osajin downregulated androgen receptor (AR) and prostate‐specific antigen (PSA) in PCa cells. Moreover, osajin suppressed PCa cell growth, migration, and invasion. Through activation of the caspase‐dependent pathway, osajin induced apoptosis in PCa cells. Conclusions These data provide a novel molecular basis of osajin in PCa cells, and cotargeting lipogenesis and the AR axis via impairment of FASN and AR expression by osajin could be applied as a new and promising approach for the treatment of malignant PCa.