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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Phytoestrogens in common herbs regulate prostate cancer cell growth in vitro
Nader S Shenouda1, Christine Zhou, Jimmy D Browning
1Department of Biochemistry and the Missouri University Center for Phytonutrient and Phytochemical Studies, University of Missouri, Columbia 65211, USA.
Abstract:
Prostate cancer is an important public health problem in the United States. Seven phytoestrogens found in common herbal products were screened for estrogen receptor binding and growth inhibition of androgen-insensitive (PC-3) and androgen-sensitive (LNCaP) human prostate tumor cells. In a competitive 3H-estradiol ligand binding assay using mouse uterine cytosol, 2.5 M quercetin, baicalein, genistein, epigallocatechin gallate (EGCG), and curcumin displaced > 85% of estradiol binding, whereas apigenin and resveratrol displaced > 40%. From growth inhibition studies in LNCaP cells, apigenin and curcumin were the most potent inhibitors of cell growth, and EGCG and baicalein were the least potent. In PC-3 cells, curcumin was the most potent inhibitor of cell growth, and EGCG was the least potent. In both cell lines, significant arrest of the cell cycle in S phase was induced by resveratrol and EGCG and in G2M phase by quercetin, baicalein, apigenin, genistein, and curcumin. Induction of apoptosis was induced by all of the 7 compounds in the 2 cell lines as shown by TUNEL and DNA fragmentation assays. Androgen responsiveness of the cell lines did not correlate with cellular response to the phytoestrogens. In conclusion, these 7 phytoestrogens, through different mechanisms, are effective inhibitors of prostate tumor cell growth.
Insights
Seven phytoestrogens from herbal products show potential in inhibiting prostate cancer cell growth. These compounds bind to estrogen receptors and induce cell cycle arrest and apoptosis in both androgen-sensitive and insensitive prostate tumor cells.
Area of Science:
- Phytochemistry
- Oncology
- Molecular Biology
Background:
- Prostate cancer represents a significant public health concern in the United States.
- Phytoestrogens, naturally occurring plant compounds, are found in many common herbal products.
- Their potential anti-cancer properties warrant investigation, particularly for prostate cancer treatment.
Purpose of the Study:
- To screen seven common phytoestrogens for their ability to bind to estrogen receptors.
- To evaluate the efficacy of these phytoestrogens in inhibiting the growth of human prostate tumor cells (PC-3 and LNCaP).
- To elucidate the mechanisms by which phytoestrogens affect prostate cancer cell proliferation and survival.
Main Methods:
- Competitive 3H-estradiol ligand binding assays were performed using mouse uterine cytosol.
- Cell growth inhibition was assessed in androgen-insensitive (PC-3) and androgen-sensitive (LNCaP) human prostate tumor cell lines.
- Cell cycle progression and apoptosis induction were analyzed using flow cytometry, TUNEL assays, and DNA fragmentation assays.
Main Results:
- Quercetin, baicalein, genistein, epigallocatechin gallate (EGCG), and curcumin demonstrated significant estrogen receptor binding (>85%).
- Curcumin and apigenin were potent growth inhibitors in LNCaP cells, while curcumin was most effective in PC-3 cells.
- All seven phytoestrogens induced apoptosis in both cell lines and caused cell cycle arrest at different phases (S or G2M).
Conclusions:
- The seven screened phytoestrogens exhibit potent anti-prostate tumor cell growth activity through various mechanisms.
- These compounds effectively inhibit estrogen receptor binding, induce cell cycle arrest, and promote apoptosis in prostate cancer cells.
- Phytoestrogens represent a promising area for further research in the development of natural anti-cancer agents for prostate cancer.
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