Epidemiological surveys indicate that intake of cruciferous vegetables is inversely related to
prostate cancer incidence, although the responsible dietary factors have not been identified. Our studies demonstrated that exposure of human
prostate cancer cells in culture to the
N-acetylcysteine (NAC) conjugate of
phenethyl isothiocyanate (
PEITC-NAC), the major metabolite of
PEITC that is abundant in watercress, inhibited proliferation and
tumorigenesis. The
PEITC-NAC is known to mediate cytoprotection at initiation of
carcinogenesis. The relevance of
PEITC-NAC in diets on the growth of prostate
tumor cells has been evaluated in immunodeficient mice with xenografted
tumors of human
prostate cancer PC-3 cells. The daily
PEITC-NAC (8 micromol/g) supplemented diet group showed a significant reduction in
tumor size in 100% of the mice during the 9-week treatment period.
Tumor weight at autopsy was reduced by 50% compared with mice on the diet without
PEITC-NAC (P = 0.05). Mitosis and in vivo
5-bromo-2'-deoxyuridine labeled proliferating cells were reduced in these
tumors. The
PEITC-NAC diet up-regulated the inhibitors of
cyclin-dependent kinases p21WAF-1/Cip-1 and p27Kip1, and reduced the expression of
cyclins D and E, indicating they were potential molecular targets. As a result, phosphorylated Rb was significantly decreased and the G1- to S-phase transition retarded. The treated
tumors also showed a significant increase in apoptosis as determined by in situ end-labeling, and by
poly ADP-ribose polymerase cleavage. This study demonstrates the first in vivo evidence of dietary
PEITC-NAC inhibiting
tumorigenesis of
prostate cancer cells.
PEITC-NAC may prevent initiation of
carcinogenesis and modulate the post-initiation phase by targeting cell cycle regulators and apoptosis induction.