title: Combination of 4-HPR and oral contraceptive in monkey model of chemoprevention of ovarian cancer.
abstract: 4-(N-hydroxyphenyl) retinamide (4-HPR) and the oral contraceptives (OCP) are currently being used alone, and in combination, for the prevention of ovarian cancer. However, the mechanism of their effects has not been studied. Non-human primate models are ideal for studying the role of these and other drugs for cancer chemoprevention because of the genetic similarity between primates and humans in respect to hormone regulation and menstrual cycle. 4-HPR and OCP were administered to sixteen female adult Macacca mulatta (Rhesus macaques) for three months alone and in combination. Laparotomy was performed before and after treatment, and ovarian biopsies were obtained to evaluate the expression of retinoid and hormone receptors, and apoptosis. ER alpha was undetectable, but ER beta, PR, RXR alpha, and RXR gamma were constitutively expressed in the ovaries. 4-HPR induced RXR alpha and RXR gamma expression at a low level and, OCP induced expression of ER beta. However, the combination of 4-HPR with OCP had a larger effect on expression of retinoid receptors. Apoptosis was detected in the 4-HPR group (equivalent dose: 200 mg/day).
authors.affiliation: Department of OB/GYN, University of Arizona, College of Medicine, Tucson, AZ 8572, USA. mbrewer@azcc.arizona.edu
authors.forename: Molly
authors.initials: M
authors.lastname: Brewer
authors.forename: James
authors.initials: J
authors.lastname: Ranger-Moore
authors.forename: William
authors.initials: W
authors.lastname: Satterfield
authors.forename: Zengping
authors.initials: Z
authors.lastname: Hao
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Emily
authors.initials: E
authors.lastname: Brewer
authors.forename: J Taylor
authors.initials: JT
authors.lastname: Wharton
authors.forename: Robert
authors.initials: R
authors.lastname: Bast
authors.forename: Changping
authors.initials: C
authors.lastname: Zou
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D003131:Combined Modality Therapy; D003276:Contraceptives, Oral / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D017313:Fenretinide / Q000494:pharmacology* / Q000627:therapeutic use; D008253:Macaca mulatta; D010051:Ovarian Neoplasms / Q000517:prevention & control*; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016588:Anticarcinogenic Agents; D003276:Contraceptives, Oral; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D017313:Fenretinide