title: Phellodendron amurense bark extract prevents progression of prostate tumors in transgenic adenocarcinoma of mouse prostate: potential for prostate cancer management.
abstract: Prostate cancer is the second leading cause of cancer-related deaths in men in Western society. Epidemiological studies suggest that a reduced risk of cancer is associated with the consumption of a phytochemical-rich diet that includes fruits and vegetables. Strategies to delay clinically significant prostate cancer will have a tremendous impact in reducing the overall incidence of prostate cancer as well as improving quality of life for elderly men. Furthermore, the long latency involved in the development of clinically significant prostate cancer provides a plethora of opportunities for its management, especially using prevention approaches. Previous studies from our laboratory show that Nexrutine (bark extract from Phellodendron amurense) prevents prostate tumor development when given prior to the development of high-grade prostatic intraepithelial neoplasia in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. In this study, we investigated the effect on the progression of established tumors in the TRAMP model by administering Nexrutine to 28-week-old TRAMP mice. Efficacy of Nexrutine was determined by histopathological evaluation of the prostate. Our data indicate that Nexrutine inhibited progression of prostate tumors that was correlated with tissue levels of transcription factors nuclear factor kappa B, cyclic-AMP response element-binding protein and phosphorylated CREB. Moreover, Nexrutine intervention resulted in a significant increase in the bone mineral density of the left femur diaphysis (p=0.009) and prevented the development of metastatic lesions. Nexrutine treatment also significantly (p=0.005) inhibited invasion of androgen-independent prostate cancer cells.
authors.affiliation: Department of Urology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Ghosh
authors.forename: Heather
authors.initials: H
authors.lastname: Graham
authors.forename: Paul
authors.initials: P
authors.lastname: Rivas
authors.forename: Xishi James
authors.initials: XJ
authors.lastname: Tan
authors.forename: Katherine
authors.initials: K
authors.lastname: Crosby
authors.forename: Shylesh
authors.initials: S
authors.lastname: Bhaskaran
authors.forename: John
authors.initials: J
authors.lastname: Schoolfield
authors.forename: Jameela
authors.initials: J
authors.lastname: Banu
authors.forename: Gabriel
authors.initials: G
authors.lastname: Fernandes
authors.forename: I-Tien
authors.initials: IT
authors.lastname: Yeh
authors.forename: Addanki P
authors.initials: AP
authors.lastname: Kumar
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001862:Bone Resorption / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D018450:Disease Progression; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D032102:Phellodendron / Q000737:chemistry; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; C512605:Nexrutine; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2