title: Xanthohumol impairs human prostate cancer cell growth and invasion and diminishes the incidence and progression of advanced tumors in TRAMP mice.
abstract: Despite recent advances in understanding the biological basis of prostate cancer, management of the disease, especially in the phase resistant to androgen ablation, remains a significant challenge. The long latency and high incidence of prostate carcinogenesis provides the opportunity to intervene with chemoprevention to prevent or eradicate prostate malignancies. In this study, we have used human hormone-resistant prostate cancer cells, DU145 and PC3, as an in vitro model to assess the efficacy of xanthohumol (XN) against cell growth, motility and invasion. We observed that treatment of prostate cancer cells with low micromolar doses of XN inhibits proliferation and modulates focal adhesion kinase (FAK) and AKT phosphorylation leading to reduced cell migration and invasion. Oxidative stress by increased production of reactive oxygen species (ROS) was associated with these effects. Transgenic adenocarcinoma of the mouse prostate (TRAMP) transgenic mice were used as an in vivo model of prostate adenocarcinoma. Oral gavage of XN, three times per week, beginning at 4 wks of age, induced a decrease in the average weight of the urogenital (UG) tract, delayed advanced tumor progression and inhibited the growth of poorly differentiated prostate carcinoma. The ability of XN to inhibit prostate cancer in vitro and in vivo suggests that XN may be a novel agent for the management of prostate cancer.
authors.affiliation: Molecular Oncology and Angiogenesis, IRCCS Azienda Ospedaliera Universitaria San Martino, IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Venè
authors.forename: Roberto
authors.initials: R
authors.lastname: Benelli
authors.forename: Simona
authors.initials: S
authors.lastname: Minghelli
authors.forename: Simonetta
authors.initials: S
authors.lastname: Astigiano
authors.forename: Francesca
authors.initials: F
authors.lastname: Tosetti
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ferrari
mesh_terms: D000284:Administration, Oral; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011427:Propiophenones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects
chemical_list: D000728:Androgens; D000970:Antineoplastic Agents; D005419:Flavonoids; D011427:Propiophenones; D017382:Reactive Oxygen Species; C104536:xanthohumol