title: Fenretinide: a novel treatment for endometrial cancer.
abstract: Resistance to progestin treatment is a major hurdle in the treatment of advanced and reoccurring endometrial cancer. Fenretinide is a synthetic retinoid that has been evaluated in clinical trials as a cancer therapeutic and chemo-preventive agent. Fenretinide has been established to be cytotoxic to many kinds of cancer cells. In the present study, we demonstrate that fenretinide decreased cell viability and induced apoptosis in Ishikawa cells, which are an endometrial cancer cell line, in dose dependent manner in-vitro. This effect was found to be independent of retinoic acid nuclear receptor signaling pathway. Further, we have shown that this induction of apoptosis by fenretinide may be caused by increased retinol uptake via STRA6. Silencing of STRA6 was shown to decrease apoptosis which was inhibited by knockdown of STRA6 expression in Ishikawa cells. Results of an in-vivo study demonstrated that intraperitoneal injections of fenretinide in endometrial cancer tumors (created using Ishikawa cells) in mice inhibited tumor growth effectively. Immunohistochemistry of mice tumors showed a decrease in Ki67 expression and an increase in cleaved caspase-3 staining after fenretinide treatment when compared to vehicle treated mice. Collectively, our results are the first to establish the efficacy of fenretinide as an antitumor agent for endometrial cancer both in-vitro and in-vivo, providing a valuable rationale for initiating more preclinical studies and clinical trials using fenretinide for the treatment of endometrial cancer.
authors.affiliation: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Navdha
authors.initials: N
authors.lastname: Mittal
authors.affiliation: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Malpani
authors.affiliation: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Dyson
authors.affiliation: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ono
authors.affiliation: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois, United States of America.
authors.forename: John S
authors.initials: JS
authors.lastname: Coon
authors.affiliation: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Julie J
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Division of Gynecology Oncology, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois, United States of America; Department of Obstetrics and Gynecology, Spectrum Health Medical Group, Grand Rapids, Michigan, United States of America.
authors.forename: Julian C
authors.initials: JC
authors.lastname: Schink
authors.affiliation: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois, United States of America; Division of Reproductive Endocrinology & Infertility, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Serdar E
authors.initials: SE
authors.lastname: Bulun
authors.affiliation: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois, United States of America; Division of Reproductive Endocrinology & Infertility, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Pavone
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D017313:Fenretinide / Q000494:pharmacology / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D019290:Megestrol Acetate / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D008819:Mice, Nude; D014801:Vitamin A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D008565:Membrane Proteins; C519685:STRA6 protein, human; D014801:Vitamin A; D017313:Fenretinide; D019290:Megestrol Acetate