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Effects of fenretinide (4-HPR) on prostate LNCaP cell growth, apoptosis, and prostate-specific gene expression
1Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595, USA.
Background:
Although fenretinide (4-HPR) is currently being evaluated in a phase II clinical study for the chemoprevention of prostate cancer [Greenwald et al.: CA 45:31-49, 1995], the mechanism underlying its antineoplastic activity has not been elucidated.
Methods:
Androgen-dependent human prostatic LNCaP cells cultured with fetal bovine serum (FBS) were treated with 4-HPR and evaluated for effects on cell growth and cell cycle phase distribution, induction of apoptosis, and changes in proliferating cell nuclear antigen (PCNA), prostate-specific antigen (PSA), and androgen receptor (AR) levels.
Results:
LNCaP cells treated with 4-HPR for 6 days showed 82-95% suppression of cell growth, with accompanying time- and dose-dependent downregulation of PCNA, a partial arrest in G1 phase of the cell cycle, and a marked increase in the percentage of apoptotic cells. Apoptosis was demonstrated by the characteristic DNA fragmentation pattern seen on agarose gels, and by flow cytometric analysis. 4-HPR-induced prostate-specific phenotype changes included significant downregulated expression of both intracellular and secreted forms of PSA, which were preceded by a reduction of AR expression.
Conclusions:
These data suggest that 4-HPR acts as a pleiotropic effector of prostate cell growth and specific gene expression.
Insights
Fenretinide (4-HPR) significantly suppresses prostate cancer cell growth by inducing apoptosis and altering cell cycle progression. This retinoid also downregulates key markers like prostate-specific antigen (PSA) and androgen receptor (AR).
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Fenretinide (4-HPR) is under investigation for prostate cancer chemoprevention.
- The precise mechanisms of 4-HPR's anti-cancer effects remain unclear.
Purpose of the Study:
- To elucidate the antineoplastic mechanism of fenretinide (4-HPR) in prostate cancer.
- To evaluate 4-HPR's impact on LNCaP cell growth, apoptosis, and specific gene expression.
Main Methods:
- Human prostate cancer LNCaP cells were treated with 4-HPR.
- Assessed effects on cell proliferation, cell cycle distribution, and apoptosis.
- Measured levels of proliferating cell nuclear antigen (PCNA), prostate-specific antigen (PSA), and androgen receptor (AR).
Main Results:
- 4-HPR treatment resulted in 82-95% suppression of LNCaP cell growth.
- Observed G1 cell cycle arrest, increased apoptosis, and downregulation of PCNA.
- 4-HPR reduced PSA and AR expression, indicating a prostate-specific phenotype change.
Conclusions:
- Fenretinide (4-HPR) exhibits pleiotropic effects on prostate cancer cells.
- 4-HPR influences both cell growth and the expression of specific genes, including AR and PSA.