Garlic constituent diallyl trisulfide prevents development of poorly differentiated prostate cancer and pulmonary metastasis multiplicity in TRAMP mice.
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.
Singh
Shivendra V
SV
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, PA, USA. singhs@upmc.edu
Powolny
Anna A
AA
Stan
Silvia D
SD
Xiao
Dong
D
Arlotti
Julie A
JA
Warin
Renaud
R
Hahm
Eun-Ryeong
ER
Marynowski
Stanley W
SW
Bommareddy
Ajay
A
Potter
Douglas M
DM
Dhir
Rajiv
R
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
D000498:Allyl Compounds; D000957:Antigens, Viral, Tumor; D015820:Cadherins; D018809:Proliferating Cell Nuclear Antigen; D013440:Sulfides; D016708:Synaptophysin; C042577:diallyl trisulfide