Flavonoid ampelopsin inhibits the growth and metastasis of prostate cancer in vitro and in mice

• Published in: PloS one Vol. 7; no. 6; p. e38802
• Main Authors: Ni, Feng, Gong, Yi, Li, Linglin, Abdolmaleky, Hamid M, Zhou, Jin-Rong
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.06.2012; Public Library of Science (PLoS)
• Subjects: AMP; Ampelopsis; Androgens; Angiogenesis; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Apoptosis - drug effects; Bcl-2 protein; Biology; Biotechnology; Bladder cancer; Body weight; Breast cancer; Cancer; Cancer metastasis; Cancer prevention; Cell cycle; Cell growth; Cell Line, Tumor; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Chemokines; CXCR4 protein; Epithelial cells; Flavonoids; Flavonoids - pharmacology; Flavonoids - therapeutic use; Food intake; Glycine max; Growth; Growth factors; Humans; Laboratories; Liver cancer; Lungs; Lymph; Lymph nodes; Lymphatic Metastasis - prevention & control; Male; Medical schools; Medicine; Melanoma; Metabolism; Metastases; Metastasis; Mice; Nutrition; Ovarian cancer; Phytochemicals; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Receptors, CXCR4 - genetics; Receptors, CXCR4 - metabolism; Rodents; Soybeans; Surgery; Tumor cell lines; Tumorigenesis; Tumors; Weight reduction; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0038802

The objective of this study was to evaluate the chemopreventive effect of a novel flavonoid, ampelopsin (AMP) on the growth and metastasis of prostate cancer cells. AMP showed the more potent activity in inhibiting the proliferation of androgen-sensitive LNCaP and, to less extent, androgen-independent PC-3 human prostate cancer cell lines in vitro, primarily by induction of apoptosis associated with down-regulation of bcl-2. On the other hand, AMP showed much less activity in inhibiting the proliferation of normal prostate epithelial cells than that of prostate cancer cell lines. AMP also inhibited the migration and invasion of PC-3 cells in vitro associated with down-regulation of CXCR4 expression. In the animal study using an orthotopic prostate tumor model, AMP (150 and 300 mg/kg body weight) inhibited the growth of PC-3 tumors and lymph node and lung metastases in a dose-dependent manner. Compared to the control mice, mice treated with AMP at 300 mg/kg BW had reduced final tumor weight by 49.2% (P<0.05), lymph node metastases by 54.5% (P = 0.3) and lung metastases by 93% (P<0.05), but had no apparent alteration on food intake or body weight. The in vivo anti-growth and anti-metastasis activities of AMP were associated with induction of apoptosis and inhibition of proliferation of prostate cancer cells, reduction of prostate tumor angiogenesis, and reduction of CXCR4 expression. Our results provide supporting evidence to warrant further investigation to develop AMP as a novel efficacious and safe candidate agent against progression and metastasis of prostate cancer.