Sulforaphane inhibits prostate carcinogenesis and pulmonary metastasis in TRAMP mice in association with increased cytotoxicity of natural killer cells

Shivendra V. Singh, Renaud Warin, Dong Xiao, A. Anna Powolny, Silvia D. Stan, Jlie A. Arlotti, Yan Zeng, Eun Ryeong Hahm, Stanley W. Marynowski, Ajay Bommareddy, Dhimant Desai, Shantu Amin, Robert A. Parise, Jan H. Beumer, William H. Chambers

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

The present study shows that oral gavage of 6 Limol D,L-sulforaphane (SFN), a synthetic analogue of cruciferous vegetable-derived L isomer, thrice per week beginning at 6 weeks of age, significantly inhibits prostate carcinogenesis and pulmonary metastasis in TRAMP mice without causing any side effects. The incidence of the prostatic intraepithelial neoplasia and well-differentiated (WD) carcinoma were ~ 23% to 28% lower (P < 0.05 compared with control by Mann-Whitney test) in the dorsolateral prostate (DLP) of SFN-treated mice compared with controls, which was not due to the suppression of T-antigen expression. The area occupied by the WD carcinoma was also ~ 44% lower in the DLP of SFN-treated mice relative to that of control mice (P = 0.0011 by Mann Whitney test). Strikingly, the SFN-treated mice exhibited-50% and 63% decrease, respectively, in pulmonary metasta-sis incidence and multiplicity compared with control mice (P < 0.05 by t test). The DLP from SFN-treated mice showed decreased cellular proliferation and increased apoptosis when compared with that from control mice. Additionally, SFN administration enhanced cytotoxicity of cocultures of natural killer (NK) cells and dendritic cells (DC) against TRAMP-Cl target cells, which correlated with infiltration of T cells in the neoplastic lesions and increased levels of interleukin-12 production by the DC. In conclusion, the results of the present study indicate that SFN administration inhibits prostate cancer progression and pulmonary metastasis in RAMP mice by reducing cell proliferation and augmenting NK cell lytic activity.

Original languageEnglish (US)
Pages (from-to)2117-2125
Number of pages9
JournalCancer Research
Volume69
Issue number5
DOIs
Publication statusPublished - Mar 1 2009

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this