Abstract
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.
Highlights
Prostate cancer is the most common invasive malignancy and the second-leading cause of cancer death in men in the U.S It is estimated that 241,740 new cases of prostate cancer would be diagnosed and about 28,170 men would die of prostate cancer in the United States in 2012 [1]
We first compared the activity among AMP, total flavonoid extract (TFE) and myricetin in inhibiting the proliferation of prostate cancer cell lines and prostate epithelial cells (PrEC)
We found that AMP significantly inhibited the proliferation of prostate cancer cell lines via apoptosis induction associated with downregulation of Bcl2 expression, Figure 3
Summary
Prostate cancer is the most common invasive malignancy and the second-leading cause of cancer death in men in the U.S It is estimated that 241,740 new cases of prostate cancer would be diagnosed and about 28,170 men would die of prostate cancer in the United States in 2012 [1]. Bioactive components in botanicals and herbal medicines may provide effective and safe candidates for chemoprevention and/or therapy of cancer. Classical Chinese medical texts contain extensive empirical records of botanical therapies used to treat patients with cancer and cancer-related systems. Most of these candidate botanical formulas are recommended based on clinical observations only. These clinical observations were almost always from uncontrolled, observational studies or anecdotal case reports. There has been limited effort to develop preclinical, mechanistic, scientific evaluation of botanical herbal products as a prerequisite for human clinical studies
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