title: Garlic constituent diallyl trisulfide prevents development of poorly differentiated prostate cancer and pulmonary metastasis multiplicity in TRAMP mice.
abstract: Identification of agents that are nontoxic but can delay onset and/or progression of prostate cancer, which is the second leading cause of cancer-related deaths among men in the United States, is highly desirable. We now show that p.o. gavage of garlic constituent diallyl trisulfide (DATS; 1 and 2 mg/day, thrice/week for 13 weeks beginning at age 8 weeks) significantly inhibits progression to poorly differentiated prostate carcinoma and pulmonary metastasis multiplicity in transgenic adenocarcinoma of mouse prostate (TRAMP) mice without any side effects. There was a trend of a decrease in average wet weights of the urogenital tract and prostate gland in 1 and 2 mg DATS-treated mice compared with controls ( approximately 25-46% decrease in DATS-treated mice compared with controls). The incidence and the area of the dorsolateral prostate occupied by the poorly differentiated carcinoma were significantly lower in both 1 and 2 mg DATS-treated mice compared with control mice. In addition, DATS administration resulted in a statistically significant decrease in pulmonary metastasis multiplicity compared with controls (P = 0.002). The dorsolateral prostate from DATS-treated TRAMP mice exhibited decreased cellular proliferation in association with induction of cyclinB1 and securin protein levels, and suppression of the expression of neuroendocrine marker synaptophysin. However, DATS administration did not have any appreciable effect on apoptosis induction, angiogenesis, or natural killer and dendritic cell function. In conclusion, the results of the present study show, for the first time, that DATS administration prevents progression to invasive carcinoma and lung metastasis in TRAMP mice.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, PA, USA. singhs@upmc.edu
authors.forename: Shivendra V
authors.initials: SV
authors.lastname: Singh
authors.forename: Anna A
authors.initials: AA
authors.lastname: Powolny
authors.forename: Silvia D
authors.initials: SD
authors.lastname: Stan
authors.forename: Dong
authors.initials: D
authors.lastname: Xiao
authors.forename: Julie A
authors.initials: JA
authors.lastname: Arlotti
authors.forename: Renaud
authors.initials: R
authors.lastname: Warin
authors.forename: Eun-Ryeong
authors.initials: ER
authors.lastname: Hahm
authors.forename: Stanley W
authors.initials: SW
authors.lastname: Marynowski
authors.forename: Ajay
authors.initials: A
authors.lastname: Bommareddy
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Potter
authors.forename: Rajiv
authors.initials: R
authors.lastname: Dhir
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000517:prevention & control*; D000498:Allyl Compounds / Q000627:therapeutic use*; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000032:analysis; D049109:Cell Proliferation / Q000187:drug effects; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D013440:Sulfides / Q000627:therapeutic use*; D016708:Synaptophysin / Q000032:analysis
chemical_list: D000498:Allyl Compounds; D000957:Antigens, Viral, Tumor; D015820:Cadherins; D018809:Proliferating Cell Nuclear Antigen; D013440:Sulfides; D016708:Synaptophysin; C042577:diallyl trisulfide