Related Experiment Video
Updated: Oct 8, 2026
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Effects of novel phenylretinamides on cell growth and apoptosis in bladder cancer
J L Clifford1, A L Sabichi, C Zou
1Department of Clinical Cancer Prevention The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. jclifford@mdanderson.org
Abstract:
Superficial bladder cancer is a major target for chemoprevention. Retinoids are important modulators of epithelial differentiation and proliferation and are effective in the treatment and prevention of several epithelial cancers. One class of compounds, the retinamides, is structurally similar to other retinoids but have the added feature of being potent apoptosis inducers. Among these, fenretinide (N-[4-hydroxyphenyl]retinamide), or 4HPR, has promise for bladder cancer chemoprevention and is currently under Phase III study in this setting. In addition to 4HPR, there are several new structurally related phenylretinamides bearing hydroxyl, carboxyl, or methoxyl residues on carbons 2, 3, and 4 of the terminal phenylamine ring [designated N-(2-hydroxyphenyl)retinamide, N-(3-hydroxyphenyl)retin amide, N-(2-carboxyphenyl)retin- amide, N-(3-carboxyphenyl)retin amide, N-(4-carboxy- phenyl)retinamide, and N-(4-methoxyphenyl)retinamide, respectively]. The objective of this study was to compare the growth inhibitory and apoptotic effects of these phenylretinamides with 4HPR in human bladder transitional cell cancer-derived cell lines of varying histological grade (RT4, grade 1; UM-UC9 and UM-UC10, grade 3; and UM-UC14, grade 4) by cell counting, cell cycle fluorescence-activated cell sorter analysis and a dual stain apoptosis assay. All of the seven phenylretinamides reduced cell number, altered the cell cycle distribution, and induced apoptosis when administered at a concentration of 10 microM, which is within the pharmacologically achievable range. Although the relative potencies of the phenylretinamides varied depending on the cell line, N-(3-hydroxy phenyl)retin- amide was the most active with significantly greater growth inhibition than 4HPR in all of the four cell lines. These in vitro findings warrant further study of these novel phenylretinamides, which may have potential as preventive or therapeutic agents in transitional cell cancer.
Insights
Novel phenylretinamides show promise for bladder cancer chemoprevention. N-(3-hydroxyphenyl)retinamide demonstrated superior growth inhibition compared to fenretinide (4HPR) in preclinical bladder cancer models.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Superficial bladder cancer necessitates effective chemoprevention strategies.
- Retinoids, including fenretinide (4HPR), are known for their roles in epithelial cell regulation and cancer treatment.
- Phenylretinamides represent a class of retinoids with potent apoptosis-inducing capabilities.
Purpose of the Study:
- To evaluate and compare the anti-cancer effects of novel phenylretinamides against fenretinide (4HPR).
- To assess the growth inhibitory and apoptotic potential of these compounds in human bladder transitional cell cancer cell lines of varying grades.
Main Methods:
- Utilized human bladder cancer cell lines (RT4, UM-UC9, UM-UC10, UM-UC14) representing different histological grades.
- Employed cell counting, fluorescence-activated cell sorter (FACS) analysis for cell cycle assessment, and dual-stain apoptosis assays.
- Administered phenylretinamides at a pharmacologically relevant concentration of 10 microM.
Main Results:
- All seven tested phenylretinamides exhibited significant growth inhibition and induced apoptosis across all tested bladder cancer cell lines.
- N-(3-hydroxyphenyl)retinamide displayed markedly enhanced growth inhibition compared to fenretinide (4HPR) in all cell lines.
- Observed alterations in cell cycle distribution were consistent with the observed cytotoxic effects.
Conclusions:
- Novel phenylretinamides possess significant in vitro anti-cancer activity against bladder transitional cell carcinoma.
- N-(3-hydroxyphenyl)retinamide emerges as a particularly promising candidate for further investigation.
- These findings support the potential of these phenylretinamides as future chemopreventive or therapeutic agents for bladder cancer.
