| Title | A dietary anthocyanidin delphinidin induces apoptosis of human prostate cancer PC3 cells in vitro and in vivo: involvement of nuclear factor-kappaB signaling. | | Author(s) | Hafeez BB, Siddiqui IA, Asim M, Malik A, Afaq F, Adhami VM, Saleem M, Din M, Mukhtar H | | Institution | Department of Dermatology, University of Wisconsin, Madison, Wisconsin 53706, USA. | | Source | Cancer Res 2008 Oct 15; 68(20):8564-72. | | MeSH | Animals
Anthocyanins
Antineoplastic Agents
Apoptosis
Cell Division
Cell Line, Tumor
Cell Proliferation
Cyclin D1
DNA
Dose-Response Relationship, Drug
G2 Phase
Humans
I-kappa B Kinase
Ki-67 Antigen
Male
Mice
Mice, Nude
NF-kappa B
Phosphorylation
Poly(ADP-ribose) Polymerases
Proliferating Cell Nuclear Antigen
Prostatic Neoplasms
Proto-Oncogene Proteins c-bcl-2
Signal Transduction
bcl-2-Associated X Protein
| | Abstract | 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, 22Rnu1, 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 G(2)-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 IkappaB kinase gamma (NEMO), (b) phosphorylation of nuclear factor-kappaB (NF-kappaB) inhibitory protein IkappaBalpha, (c) phosphorylation of NF-kappaB/p65 at Ser(536) and NF-kappaB/p50 at Ser(529), (d) NF-kappaB/p65 nuclear translocation, and (e) NF-kappaB 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-kappaB/p65, Bcl2, Ki67, and PCNA. Taken together, our data suggest that delphinidin could be developed as an agent against human PCa. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, N.I.H., Extramural
| | PubMed ID | 18922932 |
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