期刊
LIFE-BASEL
卷 12, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/life12111769
关键词
alpinumisoflavone; androgen receptor; anti-prostate cancer efficacy; apoptosis; fatty acid synthase; 3-hydroxy-3-methylglutaryl-CoA reductase; lipid and cholesterol biosynthesis
资金
- National Science and Technology Council [MOST 111-2314-B-039-035-MY3]
- National Health Research Institutes [NHRI-EX111-10901BI]
- China Medical University, Taiwan [CMU110-S-08]
Prostate cancer is the most common cancer in men. A natural product called alpinumisoflavone (AIF) has shown potential as a therapeutic remedy for prostate cancer. It reduces cell viability, migration, and invasion, and inhibits the expression of specific genes involved in cancer progression.
Prostate cancer (PCa) is the most common cancer in men, and this has been mainly noticed in Western and Asian countries. The aggregations of PCa and castration-resistant PCa (CRPC) progression are the crucial causes in the mortality of patients without the effective treatment. To seek new remedies for the lethal PCa diseases is currently an urgent need. In this study, we endeavored to investigate the therapeutic efficacy of alpinumisoflavone (AIF), a natural product, in PCa. LNCaP (androgen- sensitive) and C4-2 (CRPC) PCa cells were used. An MTT-based method, soft agar colony forming assay, biological progression approaches were applied to determine cell viability, migration, and invasion. A fatty acid quantification kit, a cholesterol detection kit and oil red O staining were conducted to analyze the intracellular levels of lipids and cholesterols. Apoptosis assays were also performed. AIF reduced cell viability, migration, and invasion in PCa cells. The expression of androgen receptor (AR), fatty acid synthase (FASN), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was substantially inhibited by AIF treatment in PCa cells. Furthermore, by inhibiting FASN and HMGCR expression, AIF decreased the amounts of intracellular fatty acids, cholesterols, and lipid droplets in PCa cells. Significantly, through coordinated targeting FASN- and HMGCR-regulated biosynthesis and the AR axis, AIF activated the caspase-associated apoptosis in PCa cells. These results collectively demonstrated for the first time the potential of AIF as a novel and attractive remedy and provided an alternative opportunity to cure PCa malignancy.
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