Alpinumisoflavone Exhibits the Therapeutic Effect on Prostate Cancer Cells by Repressing AR and Co-Targeting FASN- and HMGCR-Mediated Lipid and Cholesterol Biosynthesis

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Title:	Alpinumisoflavone Exhibits the Therapeutic Effect on Prostate Cancer Cells by Repressing AR and Co-Targeting FASN- and HMGCR-Mediated Lipid and Cholesterol Biosynthesis
Authors:	Basavaraj, Praveenkumar Ruangsai, Phakkhathorn Hsieh, Po-Fan Jiang, Wen-Ping Bau, Da-Tian Huang, Guan-Jhong Huang, Wen-Chin
Contributors:	China Medical University Taiwan China Medical University Taiwan China Medical University Taiwan China Medical University Hospital - Taiwan CDepartment of Pharmacy, Chia Nan University of Pharmacy & Science China Medical University Taiwan China Medical University Hospital - Taiwan Asia University Taiwan China Medical University Taiwan
Keywords:	fatty-acid synthase androgen receptor apoptosis progression lipogenesis inhibition activation growth
Date:	2022
Issue Date:	2023-12-11 14:02:09 (UTC+8)
Publisher:	MDPI
Abstract:	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.
Relation:	LIFE-BASEL, v.12, n.11, 1769
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

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