title: Antiproliferative and Antiestrogenic Activities of Bonediol an Alkyl Catechol from Bonellia macrocarpa.
abstract: The purpose of this study was to investigate antiproliferative activity of bonediol, an alkyl catechol isolated from the Mayan medicinal plant Bonellia macrocarpa. Bonediol was assessed for growth inhibition of androgen-sensitive (LNCaP), androgen-insensitive (PC-3), and metastatic androgen-insensitive (PC-3M) human prostate tumor cells; toxicity on normal cell line (HEK 293) was also evaluated. Hedgehog pathway was evaluated and competitive 3H-estradiol ligand binding assay was performed. Additionally, antioxidant activity on Nrf2-ARE pathway was evaluated. Bonediol induced a growth inhibition on prostate cancer cell lines (IC50 from 8.5 to 20.6 µM). Interestingly, bonediol binds to both estrogen receptors (ERα (2.5 µM) and ERβ (2.1 µM)) and displaces the native ligand E2 (17β-estradiol). No significant activity was found in the Hedgehog pathway. Additionally, activity of bonediol on Nrf2-ARE pathway suggested that bonediol could induce oxidative stress and activation of detoxification enzymes at 1 µM (3.8-fold). We propose that the compound bonediol may serve as a potential chemopreventive treatment with therapeutic potential against prostate cancer.
authors.affiliation: Unidad de Investigación Médica Yucatán, Unidad Médica de Alta Especialidad, Centro Médico Ignacio García Téllez, Instituto Mexicano del Seguro Social (IMSS), Calle 41 No. 439, Colonia Industrial, 97150 Mérida, YUC, Mexico.
authors.forename: Rosa
authors.initials: R
authors.lastname: Moo-Puc
authors.affiliation: Unidad de Biotecnología, Centro de Investigación Científica de Yucatán (CICY), Calle 43 No. 130, Colonia Chuburná de Hidalgo, 97200 Mérida, YUC, Mexico.
authors.forename: Edgar
authors.initials: E
authors.lastname: Caamal-Fuentes
authors.affiliation: Unidad de Biotecnología, Centro de Investigación Científica de Yucatán (CICY), Calle 43 No. 130, Colonia Chuburná de Hidalgo, 97200 Mérida, YUC, Mexico.
authors.forename: Sergio R
authors.initials: SR
authors.lastname: Peraza-Sánchez
authors.affiliation: Department of Biochemistry, University of Missouri, 117 Schweitzer Hall, Columbia, MO 65211, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Slusarz
authors.affiliation: Nebraska College of Technical Agriculture Veterinary Technology Program, 404 East 7th Street, Curtis, NE 69025, USA.
authors.forename: Glenn
authors.initials: G
authors.lastname: Jackson
authors.affiliation: Lindenwood University Belleville, 2600 W. Main, Belleville, IL 62226, USA.
authors.forename: Sara K
authors.initials: SK
authors.lastname: Drenkhahn
authors.affiliation: Department of Biochemistry, University of Missouri, 117 Schweitzer Hall, Columbia, MO 65211, USA.
authors.forename: Dennis B
authors.initials: DB
authors.lastname: Lubahn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D020847:Estrogen Receptor Modulators / Q000737:chemistry / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D029623:Primulaceae / Q000737:chemistry*; D011869:Radioligand Assay; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002396:Catechols; D020847:Estrogen Receptor Modulators; D010936:Plant Extracts; D011960:Receptors, Estrogen