A Dietary Anthocyanidin Delphinidin Induces Apoptosis of Human Prostate Cancer PC3 Cells In vitro and In vivo : Involvement of Nuclear Factor-κB Signaling

• Published in: Cancer research (Chicago, Ill.) Ill.), 2008-10, Vol.68 (20), p.8564-8572
• Main Authors: Hafeez, Bilal Bin, Siddiqui, Imtiaz Ahmad, Asim, Mohammad, Malik, Arshi, Afaq, Farrukh, Adhami, Vaqar Mustafa, Saleem, Mohammad, Din, Maria, Mukhtar, Hasan
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-08-2232

Delphinidin, a major anthocyanidin present in many pigmented fruits and vegetables, possesses antioxidant, anti-inflammatory, and antiangiogenic properties. In this study, we provide evidence that it could be developed as a novel agent against human prostate cancer (PCa). We observed that delphinidin treatment to human PCa LNCaP, C4-2, 22Rν1, and PC3 cells resulted in a dose-dependent inhibition of cell growth without having any substantial effect on normal human prostate epithelial cells. We selected PC3 cells as a test model system because of their highly aggressive proliferative nature. Delphinidin treatment of cells resulted in a dose-dependent induction of apoptosis and arrest of cells in G2-M phase. This induction of apoptosis seems to be mediated via activation of caspases because N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluromethylketone significantly reduced apoptosis induced by delphinidin. We also observed that delphinidin treatment of cells resulted in a dose-dependent decrease in (a) phosphorylation of IκB kinase γ (NEMO), (b) phosphorylation of nuclear factor-κB (NF-κB) inhibitory protein IκBα, (c) phosphorylation of NF-κB/p65 at Ser536 and NF-κB/p50 at Ser529, (d) NF-κB/p65 nuclear translocation, and (e) NF-κB DNA binding activity. Delphinidin administration (2 mg, i.p. thrice weekly) to athymic nude mice implanted with PC3 cells resulted in a significant inhibition of tumor growth. Analysis of tumors from delphinidin-treated mice showed significant decrease in the expression of NF-κB/p65, Bcl2, Ki67, and PCNA. Taken together, our data suggest that delphinidin could be developed as an agent against human PCa. [Cancer Res 2008;68(20):8564–72]