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Fenretinide:A Potential Treatment for Endometriosis

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Abstract

Objective

Fenretinide is a synthetic retinoid analogue that promotes apoptosis but has decreased toxicity when compared to other retinoids. We have previously shown that retinoic acid (RA) production in endometriotic tissue is decreased, resulting in reduced estrogen metabolism and apoptotic resistance. We hypothesize fenretinide may induce apoptosis in endometriotic cells and tissues, thereby reducing disease burden.

Materials and Methods

Primary endometriotic stromal cells were collected, isolated, cultured, and treated with fenretinide in doses from 0 to 20 p,mol/L. Cell count, viability, and immunoblots were per-formed to examine apoptosis. Quantitative reverse transcription-polymerase chain reaction from endometriotic cells treated with fenretinide was used to examine expression of genes involved in RA signaling including stimulated by RA 6 (STRA6), cellular RA binding protein 2 (CRABP2), and fatty acid binding protein 5 (FABP5). Endometriotic tissue was xenografted subcutaneously into the flanks of mice which were treated with fenretinide for 2 weeks, after which the mice were killed and lesion volumes calculated. Statistical analysis was performed using ttestand analysis ofvariance.

Results

Treatment with fenretinide significantly decreased total cell count (doses 5-20 p,L) and viability (doses 10-20 p,mol/L). Fenretinide increased protein levels of the apoptotic marker poly (ADP ribose) polymerase (starting at 10 p,mol/L) and decreased proliferation marker proliferating cell nuclear antigen (10 μmol/L, starting at 8-day treatment). Examination of genes involved in retinoid uptake and action showed that treatment induced STRA6 expression while expression of CRABP2 and FABP5 remained unchanged. Fenretinide also significantly decreased the endometriotic lesion xenograft volume.

Conclusions

Fenretinide increases STRA6 expression thereby potentially reversing the pathological loss of retinoid availability. Treatment with this Compound induces apoptosis. In vivo treatments decrease lesion volume. Targeting the RA signaling pathway may be a promising novel treatment for women with endometriosis.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, 259 E. Erie, Suite 2400, Chicago, IL, 60611, USA

    Mary Ellen Pavone MD, MSc, Saurabh S. Malpani MS, Matthew Dyson PhD, J. Julie Kim & Serdar E. Bulun MD

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  1. Mary Ellen Pavone MD, MSc
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  2. Saurabh S. Malpani MS
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  3. Matthew Dyson PhD
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  4. J. Julie Kim
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  5. Serdar E. Bulun MD
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Correspondence to Mary Ellen Pavone MD, MSc.

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Pavone, M.E., Malpani, S.S., Dyson, M. et al. Fenretinide:A Potential Treatment for Endometriosis. Reprod. Sci. 23, 1139–1147 (2016). https://doi.org/10.1177/1933719116632920

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