N-(4-hydroxyphenyl)retinamide (4-HPR) decreases neoplastic properties of human prostate cells: an agent for
R M Sharp1, D Bello-DeOcampo, S T Quader
1Department of Zoology, S-350 Plant Biology Building, Michigan State University, East Lansing, MI 48824-1312, USA.
Abstract:
The development of prostate cancer through a multistep process of carcinogenesis may have a long latent period of 20-30 years. It is possible that progression to a malignant state could be blocked or reversed during this time. This study focuses on the ability of the synthetic retinoid, N-(4-hydroxyphenyl)-retinamide (4-HPR), to reverse changes associated with malignant transformation and tumor progression, towards a normal phenotype. To examine the responsiveness of cells at different steps of prostate carcinogenesis, three immortalized, but non-tumorigenic (RWPE-1, WPE1-7 and WPE1-10), and one human prostate carcinoma cell line (DU-145), were used. The effects of 4-HPR on cell proliferation, expression of intermediate filament proteins cytokeratin 18 and vimentin, and tumor suppressor proteins p53 and pRb were examined by immunostaining and compared. Results show that 4-HPR caused inhibition of growth in all cell lines in a dose-dependent manner. 4-HPR induced an increase in staining for cytokeratin 18, a marker of differentiation for prostate epithelial cells. While all cell lines showed strong immunostaining for vimentin, treatment with 4-HPR for 8 days caused a marked decrease in staining for vimentin in all cell lines. In an in vitro assay, 4-HPR also caused inhibition of invasion by DU-145 cells in a dose-dependent manner. Furthermore, 4-HPR treatment was effective in significantly decreasing the abnormal nuclear staining for the tumor suppressor proteins p53 and pRb. Because 4-HPR decreased invasion-associated vimentin expression, inhibited invasion, and normalized p53 and pRb immunostaining, we propose that 4-HPR may be an effective agent for secondary and tertiary prevention, i.e. promotion and progression stages, respectively, of prostate cancer.
Insights
The synthetic retinoid N-(4-hydroxyphenyl)-retinamide (4-HPR) inhibits prostate cancer cell growth and invasion. It also normalizes tumor suppressor proteins, suggesting potential for cancer prevention during promotion and progression stages.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Prostate cancer develops over decades, offering a window for intervention.
- Synthetic retinoids like N-(4-hydroxyphenyl)-retinamide (4-HPR) may reverse malignant changes.
Purpose of the Study:
- To evaluate 4-HPR's efficacy in reversing malignant transformation in prostate cells.
- To assess 4-HPR's impact on cell proliferation, differentiation, invasion, and tumor suppressor proteins.
Main Methods:
- Utilized immortalized non-tumorigenic (RWPE-1, WPE1-7, WPE1-10) and carcinoma (DU-145) prostate cell lines.
- Examined effects of 4-HPR on cell growth, cytokeratin 18, vimentin, p53, and pRb expression via immunostaining.
- Assessed 4-HPR's effect on DU-145 cell invasion in vitro.
Main Results:
- 4-HPR dose-dependently inhibited growth in all tested cell lines.
- Treatment increased cytokeratin 18 (differentiation marker) and decreased vimentin (invasion marker) expression.
- 4-HPR reduced DU-145 cell invasion and normalized abnormal p53 and pRb nuclear staining.
Conclusions:
- 4-HPR demonstrates potential as an agent for secondary and tertiary prostate cancer prevention.
- The compound may reverse key changes associated with tumor promotion and progression.
