Related Experiment Videos
Anticancer effects of fenretinide in human medulloblastoma
C Damodar Reddy1, Asha Guttapalli, Peter C Adamson
1Division of Neuro-Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. reddyd@email.chop.edu
Abstract:
N-(4-hydroxyphenyl) retinamide (4-HPR, fenretinide) a synthetic retinoid is in clinical trials for the treatment of several malignancies. However, its biological effects and therapeutic value in childhood brain tumor medulloblastoma (MB) has not been investigated. In this study, we report for the first time that fenretinide (2.5-10 microM) induces apoptotic cell death in human MB cells. We observed significant inhibition of cell survival in four MB cell lines (D425MED, D458MED, D283MED and D341MED) as determined by MTT assays. These results were further supported by inhibition of anchorage-independent colony formation in soft agar. Fenretinide-induced decrease in cell viability was in part due to activation of caspase-3 dependent cell death, which was further supported by the cleavage of poly(ADP-ribose) polymerase-1 (PARP-1), a caspase-3 substrate. Cell death was partially prevented by the antioxidant, l-ascorbic acid suggesting that free radical intermediates might be involved in fenretinide effects. These results suggest that pharmacologically achievable concentrations of fenretinide are effective in killing MB cells and thus show its therapeutic potential to treat human MB.
Insights
Fenretinide, a synthetic retinoid, effectively induces cell death in medulloblastoma (MB) cells. This study highlights its potential as a therapeutic agent for treating this childhood brain tumor.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- N-(4-hydroxyphenyl) retinamide (4-HPR, fenretinide) is a synthetic retinoid investigated for various cancers.
- The therapeutic potential of fenretinide in medulloblastoma (MB), a common childhood brain tumor, remains unexplored.
Purpose of the Study:
- To investigate the biological effects and therapeutic potential of fenretinide in human medulloblastoma cells.
- To determine if fenretinide can induce cell death and inhibit survival in MB cell lines.
Main Methods:
- Utilized MTT assays to assess cell viability and survival.
- Evaluated anchorage-independent colony formation in soft agar.
- Assessed caspase-3 activation and poly(ADP-ribose) polymerase-1 (PARP-1) cleavage.
Main Results:
- Fenretinide (2.5-10 microM) significantly inhibited cell survival in four human MB cell lines.
- Observed inhibition of anchorage-independent colony formation.
- Demonstrated fenretinide-induced apoptosis via caspase-3 activation and PARP-1 cleavage.
- Identified a partial protective effect of l-ascorbic acid, suggesting a role for free radicals.
Conclusions:
- Pharmacologically achievable concentrations of fenretinide are effective in inducing cell death in human medulloblastoma cells.
- Fenretinide exhibits therapeutic potential for treating human medulloblastoma.
- The mechanism involves caspase-3 dependent apoptosis, potentially mediated by free radical intermediates.
Related Concept Videos
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Targeted Cancer Therapies
There are several types of targeted therapies against specific...
Drugs that Stabilize Microtubules