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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Sulforaphane and its metabolite mediate growth arrest and apoptosis in human prostate cancer cells
J W Chiao1, F-L Chung, R Kancherla
1Department of Medicine, New York Medical College, Valhalla, NY 10595, USA.
Abstract:
The relation between the consumption of cruciferous vegetables and reduced prostate cancer occurrence has been documented, although the responsible phytochemicals are unknown. The effects of sulforaphane (SFN) which occurs as the precursor glucosinolate in broccoli and other cruciferous vegetables, and its metabolite N-acetylcysteine conjugate (SFN-NAC) on prostate cancer cells were investigated. SFN and SFN-NAC were analyzed with the androgen-dependent human prostate cancer LNCaP cell line model. Cell growth and apoptosis were determined with the expression of androgen receptor and prostate specific antigen, DNA synthesis, cell cycle progression, DNA strand breaks and caspase activation to ascertain the effects and mechanism. SFN and SFN-NAC were demonstrated for the first time to mediate a dose-dependent apoptosis and growth arrest in the prostate cancer cells. Caspases were activated and DNA strand breaks were detected in apoptotic cells. The expression of phosphorylated and dephosphorylated androgen receptors, and the production of prostate specific antigen were attenuated. The expression of cyclin D1 and DNA synthesis were inhibited along with G1 cell cycle block, causing decreased cell density and growth. SFN and its metabolite SFN-NAC have similar activities to induce growth arrest and apoptosis, indicating that the effects of SFN are maintained through the metabolic processes. SFN as a dietary component of cruciferous vegetables active in the prevention of prostate cancer is discussed.
Insights
Sulforaphane (SFN) and its metabolite SFN-NAC from cruciferous vegetables induce prostate cancer cell death and growth arrest. These compounds show similar activity, suggesting SFN
Area of Science:
- Oncology
- Nutritional Science
- Biochemistry
Background:
- Reduced prostate cancer incidence is linked to cruciferous vegetable consumption.
- The specific phytochemicals responsible for this effect remain unidentified.
Purpose of the Study:
- To investigate the effects of sulforaphane (SFN) and its metabolite SFN-N-acetylcysteine conjugate (SFN-NAC) on prostate cancer cells.
- To elucidate the mechanisms by which SFN and SFN-NAC influence prostate cancer cell growth and apoptosis.
Main Methods:
- Utilized the androgen-dependent human prostate cancer LNCaP cell line model.
- Assessed cell growth, apoptosis, androgen receptor and prostate specific antigen expression, DNA synthesis, cell cycle progression, DNA strand breaks, and caspase activation.
Main Results:
- SFN and SFN-NAC demonstrated dose-dependent induction of apoptosis and growth arrest in prostate cancer cells.
- Activated caspases and detected DNA strand breaks in apoptotic cells.
- Attenuated androgen receptor and prostate specific antigen expression, inhibited cyclin D1 and DNA synthesis, and induced G1 cell cycle arrest.
Conclusions:
- SFN and its metabolite SFN-NAC exhibit similar anti-cancer activities, indicating SFN's effects are maintained through metabolic processes.
- SFN is a potent dietary component in cruciferous vegetables with significant potential in prostate cancer prevention.
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