Anticancer effects of fenretinide in human medulloblastoma

C. Damodar Reddy; Asha Guttapalli; Peter C. Adamson; Mohan C. Vemuri; Donald O'Rourke; Leslie N. Sutton; Peter C. Phillips

doi:10.1016/j.canlet.2005.02.013

Anticancer effects of fenretinide in human medulloblastoma

C. Damodar Reddy, Asha Guttapalli, Peter C. Adamson, Mohan C. Vemuri, Donald O'Rourke, Leslie N. Sutton, Peter C. Phillips

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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 μM) 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.

Original language	English
Pages (from-to)	262-269
Number of pages	8
Journal	Cancer Letters
Volume	231
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2005.02.013
State	Published - 18 Jan 2006
Externally published	Yes

Keywords

Apoptosis
Caspase-3
Fenretinide
Medulloblastoma

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10.1016/j.canlet.2005.02.013

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title = "Anticancer effects of fenretinide in human medulloblastoma",

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 μM) 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.",

keywords = "Apoptosis, Caspase-3, Fenretinide, Medulloblastoma",

author = "\{Damodar Reddy\}, C. and Asha Guttapalli and Adamson, \{Peter C.\} and Vemuri, \{Mohan C.\} and Donald O'Rourke and Sutton, \{Leslie N.\} and Phillips, \{Peter C.\}",

note = "Funding Information: This project is supported by grants from Children's Brain Tumor Foundation, New York and Childhood Brain Tumor Foundation, Washington, DC to CDR. We thank Dr Darell D. Bigner for providing the human MB cell lines. We are thankful to NCI and R. W. Johnson Foundation for supplying fenretinide.",

year = "2006",

month = jan,

day = "18",

doi = "10.1016/j.canlet.2005.02.013",

language = "English",

volume = "231",

pages = "262--269",

journal = "Cancer Letters",

issn = "0304-3835",

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number = "2",

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TY - JOUR

T1 - Anticancer effects of fenretinide in human medulloblastoma

AU - Damodar Reddy, C.

AU - Guttapalli, Asha

AU - Adamson, Peter C.

AU - Vemuri, Mohan C.

AU - O'Rourke, Donald

AU - Sutton, Leslie N.

AU - Phillips, Peter C.

N1 - Funding Information: This project is supported by grants from Children's Brain Tumor Foundation, New York and Childhood Brain Tumor Foundation, Washington, DC to CDR. We thank Dr Darell D. Bigner for providing the human MB cell lines. We are thankful to NCI and R. W. Johnson Foundation for supplying fenretinide.

PY - 2006/1/18

Y1 - 2006/1/18

N2 - 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 μM) 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.

AB - 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 μM) 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.

KW - Apoptosis

KW - Caspase-3

KW - Fenretinide

KW - Medulloblastoma

UR - https://www.scopus.com/pages/publications/29844431881

U2 - 10.1016/j.canlet.2005.02.013

DO - 10.1016/j.canlet.2005.02.013

M3 - Article

C2 - 16399227

AN - SCOPUS:29844431881

SN - 0304-3835

VL - 231

SP - 262

EP - 269

JO - Cancer Letters

JF - Cancer Letters

IS - 2

ER -

Anticancer effects of fenretinide in human medulloblastoma

Abstract

Keywords

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