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Osajin displays potential antiprostate cancer efficacy via impairment of fatty acid synthase and androgen receptor expression
Author(s) -
Huang ShihYin,
Huang GuanJhong,
Hsieh PoFan,
Wu HsiChin,
Huang WenChin
Publication year - 2019
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23876
Subject(s) - lipogenesis , fatty acid synthase , androgen receptor , lncap , bicalutamide , prostate cancer , cancer research , androgen deprivation therapy , propidium iodide , endocrinology , apoptosis , chemistry , fatty acid , medicine , biology , cancer , biochemistry , programmed cell death , lipid metabolism
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.