Cell lines

T-ALL cell lines, CCRF-CEM leukemia cells, CCRF-CEM and Jurkat cell, OVCAR-5 cell

Preparation method

The solubility of this compound in DMSO is > 19.6 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

>1 μM, 3 days

Applications

Fenretinide inhibited the growth of many tumor cells, including small-cell lung cancer, malignant hemopoietic cells, and breast cancer cells. The IC50 values of Fenretinide were 0.3 and 0.4 μM in 222 and UCI 101 ovarian cancer cell lines. Fenretinide showed antitumor activity in selected T-ALL cell lines. Fenretinide inhibited DES activity in CCRF-CEM leukemia cells in a dose and time dependent manner, leading to a concomitant increase of the endogenous cellular dhCer content. Fenretinide (3 μM) induced dhCer accumulation in both CCRF-CEM and Jurkat cells. Fenretinide (> 1 μM) inhibited OVCAR-5 cell proliferation and viability, with 70-90% growth inhibition at 10 μM. Fenretinide (1 μM) significantly inhibited OVCAR-5 invasion after 3 days preincubation.

Animal models

HFD-fed male C57Bl/6 mice, NOD/SCID mice

Dosage form

Intraperitoneal injection, 10 mg/kg

Application

Fenretinide (10 mg/kg, i.p.) selectively inhibited ceramide accumulation HFD-fed male C57Bl/6 mice. Fenretinide treatment improved glucose tolerance and insulin sensitivity. Addition of 25 mg/kg ketoconazole to Fenretinide in NOD/SCID mice increased 4-HPR plasma levels.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Fenretinide(4HPR) is an inhibitor of Focal adhesion kinase (FAK) [1].

Fenretinideis a vitamin A analogue, it has been shown toinhibit the growth of many tumor cells, including small-cell lung cancer, malignant hemopoietic cells, and breast cancer cells. Fenretinide may also protectwomen against the development of ovarian cancer. The effect of Fenretinide on several gynecologic cancer cell lines shows the IC50 values of Fenretinide are only 0.3 and 0.4μM in two ovarian cancer cell lines(222and UCI 101) and are from 1 to 10μM in other ovarian cancer cell lines and cervical, endometrial cancer cell lines [2].

Fenretinide has also been shown to induce apoptosis inhuman prostate carcinoma cells (HPC).The IC50s of Fenretinide in LNCaP, DU145, and PC-3 are 0.9±0.16μM, 4.4±0.45μM and 3.0±1.0μM,respectively.Fenretinide induces this apoptosis through increasingROS and increasing enzymatic labeling of DNA breaks and formation of a DNA ladder. It is also reported that Fenretinide can impair prostate cancer cell migration and invasion by interfering with FAK/AKT/GSK3β pathway and β-catenin stability [1, 3].

References:
[1] Roberto Benelli, Stefano Monteghirfo, Roberta Venè, Francesca Tosettiand Nicoletta Ferrari.The chemopreventive retinoid 4HPR impairs prostate cancer cell migration and invasion by interfering with FAK/AKT/GSK3β pathway andβ-catenin stability. Molecular Cancer.2010, 9:142-154.
[2] Anita L. Sabichi, Denver T. Hendricks, Mary A. Bober, Michael J. Birrer. Retinoic acid receptorβexpression and growthinhibition of gynecologic cancer cells by thesynthetic retinoidn-(4-hydroxyphenyl) retinamide. Journal of the National Cancer Institute. 1998, 90(8): 597-605.
[3] Shi-Yong Sun, Ping Yue, and Reuben Lotan. Induction of apoptosis by n-(4-hydroxyphenyl)retinamide andits association with reactive oxygen species, nuclearretinoic acid receptors, and apoptosis-related genes in human prostate carcinoma cells.Molecular Pharmacology. 1999, 55:403–410.