A Novel Flavonoid Composition Targets Androgen Receptor Signaling and Inhibits Prostate Cancer Growth in Preclinical Models

The high prevalence and long latency period of prostate cancer (PCa) provide a unique opportunity to control disease progression with dietary and nutraceutical approaches. We developed ProFine, a standardized composition of luteolin, quercetin, and kaempferol, and investigated its potential as a nutraceutical for PCa in preclinical models. The three ingredients of ProFine demonstrated synergistic in vitro cytotoxicity and effectively induced apoptosis in PCa cells. ProFine markedly affected the transcriptome of PCa cells, suppressed the expression of androgen receptor, and inhibited androgen-regulated genes. Oral administration of ProFine did not exhibit obvious toxicities in mice, and the three ingredients retained their individual pharmacokinetic and bioavailability profiles. Importantly, ProFine significantly retarded the growth of PCa xenografts in athymic nude mice and extended the survival of animals. This study provides preclinical evidence supporting the promise of ProFine as a safe, efficacious, and affordable intervention to control PCa progression and improve clinical outcomes.

Neoplasia (New York, N.Y.). 2018 Jul 04 [Epub ahead of print]

Kenza Mamouni, Shumin Zhang, Xin Li, Yanhua Chen, Yang Yang, Jaeah Kim, Michael G Bartlett, Ilsa M Coleman, Peter S Nelson, Omer Kucuk, Daqing Wu

Molecular Oncology and Biomarkers Program, Georgia Cancer Center; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA., Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA., Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, USA., Division of Human Biology, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA., Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA., Molecular Oncology and Biomarkers Program, Georgia Cancer Center; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA; Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA; MetCure Therapeutics LLC, Atlanta, GA, USA. Electronic address: .

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