Fenretinide (4-HPR) is a synthetic retinoid deriverative, binding to the retinoic acid receptors (RAR) at concentrations necessary to induce cell death.Fenretinide (4-HPR) demonstrates both immediate and prolonged antitumor effects in specific T-ALL cell lines. It suppresses DES activity in CCRF-CEM leukemia cells dependent on dosage and duration, resulting in increased levels of endogenous cellular dhCer. A rise in dhCer levels is observed in both CCRF-CEM and Jurkat cells with Fenretinide treatment at 3 µM[1]. Ceramide inhibition with fenretinide protects insulin signaling, which prevents lipid-induced reductions in insulin-stimulated glucose uptake[2]. When applied at concentrations over 1 µM, Fenretinide impedes OVCAR-5 cell growth and survival, achieving 70-90% growth suppression at 10 µM. Preincubation with Fenretinide at 1 µM notably reduces OVCAR-5 cell invasion over three days. Furthermore, endothelial cells exposed to 1 µM of 4-HPR do not form tubular structures, instead forming small cell clusters[4].
体内研究
Administered at 10 mg/kg intraperitoneally, Fenretinide specifically counters ceramide buildup in HFD-fed male C57Bl/6 mice, enhancing glucose tolerance and insulin sensitivity as evidenced by glucose and insulin tolerance tests[2].
The administration of 25 mg/kg ketoconazole with Fenretinide in NOD/SCID mice raises the plasma levels of 4-HPR[3].
体外研究
Fenretinide (4-HPR) is a synthetic retinoid deriverative, binding to the retinoic acid receptors (RAR) at concentrations necessary to induce cell death.Fenretinide (4-HPR) demonstrates both immediate and prolonged antitumor effects in specific T-ALL cell lines. It suppresses DES activity in CCRF-CEM leukemia cells dependent on dosage and duration, resulting in increased levels of endogenous cellular dhCer. A rise in dhCer levels is observed in both CCRF-CEM and Jurkat cells with Fenretinide treatment at 3 µM[1].
Ceramide inhibition with fenretinide protects insulin signaling, which prevents lipid-induced reductions in insulin-stimulated glucose uptake[2].
When applied at concentrations over 1 µM, Fenretinide impedes OVCAR-5 cell growth and survival, achieving 70-90% growth suppression at 10 µM. Preincubation with Fenretinide at 1 µM notably reduces OVCAR-5 cell invasion over three days. Furthermore, endothelial cells exposed to 1 µM of 4-HPR do not form tubular structures, instead forming small cell clusters[4].
all-trans-N-(4-Hydroxyphenyl)retinamide/酚维A胺 细胞实验
Cell Line
Concentration
Treated Time
Description
References
TUBO cells
5µM to 100µM
72 h
To evaluate the effect of Bio-nFeR on TUBO cell viability, showing a dose-dependent inhibition of cell viability.
J Exp Clin Cancer Res. 2024 Nov 5;43(1):296.
MDA-MB-231 cells
5µM to 100µM
72 h
To evaluate the effect of Bio-nFeR on MDA-MB-231 cell viability, showing a dose-dependent inhibition of cell viability.
J Exp Clin Cancer Res. 2024 Nov 5;43(1):296.
MCF7 cells
5µM to 100µM
72 h
To evaluate the effect of Bio-nFeR on MCF7 cell viability, showing a dose-dependent inhibition of cell viability.
J Exp Clin Cancer Res. 2024 Nov 5;43(1):296.
RAW 264.7 cells
0.1, 1, 10 μM
Fenretinide dose-dependently reduced M1 polarization in LOP-treated RAW 264.7 cells and decreased mRNA expression of M1 markers (iNos and Cox2) and pro-inflammatory cytokines (Tnfa and Il1b).
Acta Pharm Sin B. 2023 Jan;13(1):142-156.
Rh30 cells
4 μM
48 h
To investigate the mechanism of Fenretinide-induced cell death, results showed that Fenretinide induces cell death through ROS production and cytoplasmic vacuolization
Cell Death Differ. 2020 Aug;27(8):2500-2516.
Rh4 cells
3 μM
48 h
To investigate the mechanism of Fenretinide-induced cell death, results showed that Fenretinide induces cell death through ROS production and cytoplasmic vacuolization
Cell Death Differ. 2020 Aug;27(8):2500-2516.
human airway smooth-muscle cells
5 μM
5 h
To evaluate the effects of Fenretinide on sphingolipid metabolites in airway smooth-muscle cells. Results showed that Fenretinide increased sphinganine and dihydroceramides, and decreased intracellular calcium concentration.
Am J Respir Cell Mol Biol. 2020 Nov;63(5):690-698.
human lung alveolar epithelial cell line A549
5 μM
5 h
To evaluate the effects of Fenretinide on sphingolipid metabolites in lung cells. Results showed that Fenretinide increased sphinganine and dihydroceramides.
Am J Respir Cell Mol Biol. 2020 Nov;63(5):690-698.
Rat lung goblet cell line
1.25 µM
Selectively prevents MUC5AC overexpression without significantly affecting MUC5B expression
Cell Mol Life Sci. 2020 Nov;77(21):4255-4267.
CFBE 41o- cells
1.25 µM
Selectively prevents MUC5AC overexpression without significantly affecting MUC5B expression
Cell Mol Life Sci. 2020 Nov;77(21):4255-4267.
MCF7 cells
5 μM
4 h
Evaluate the effect of Fenretinide on CERK activity, found it suppresses NBD-C6-C1P production
J Lipid Res. 2024 Aug;65(8):100584.
all-trans-N-(4-Hydroxyphenyl)retinamide/酚维A胺 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
129 Sv mice
HER2/neu transgenic mouse model
Oral gavage
100 mg/kg
5 days/week, from week 14 to week 32 post-birth
To evaluate the effect of Bio-nFeR on mammary tumorigenesis and metastasis in HER2/neu transgenic mice, showing significant inhibition of tumor occurrence and metastasis.
J Exp Clin Cancer Res. 2024 Nov 5;43(1):296.
Mice
CFTR knockout mice
5–10 mg/kg
Not mentioned
Corrects pro-inflammatory lipid imbalance by decreasing AA levels and upregulating DHA levels
Cell Mol Life Sci. 2020 Nov;77(21):4255-4267.
Sprague-Dawley rats
Subcutaneous implantation model
Subcutaneous injection
5% w/w
1 month
Evaluate the in vivo release properties of PLGA-PVP-4HPR implants, showing that TEAC-PVP-4HPR PLGA implants achieved nearly complete release of 4HPR over 1 month
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