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 Citations (Scopus)

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
StatePublished - Mar 1 2009

Fingerprint

Natural Killer Cells
Prostate
Carcinogenesis
Neoplasm Metastasis
Lung
Dendritic Cells
Cell Proliferation
Prostatic Intraepithelial Neoplasia
Carcinoma
sulforafan
Viral Tumor Antigens
Incidence
Interleukin-12
Coculture Techniques
Vegetables
Prostatic Neoplasms
Apoptosis
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Singh, Shivendra V. ; Warin, Renaud ; Xiao, Dong ; Powolny, A. Anna ; Stan, Silvia D. ; Arlotti, Jlie A. ; Zeng, Yan ; Hahm, Eun Ryeong ; Marynowski, Stanley W. ; Bommareddy, Ajay ; Desai, Dhimant ; Amin, Shantu ; Parise, Robert A. ; Beumer, Jan H. ; Chambers, William H. / Sulforaphane inhibits prostate carcinogenesis and pulmonary metastasis in TRAMP mice in association with increased cytotoxicity of natural killer cells. In: Cancer Research. 2009 ; Vol. 69, No. 5. pp. 2117-2125.
@article{f2b2f6a5378e42b69468429063f8345b,
title = "Sulforaphane inhibits prostate carcinogenesis and pulmonary metastasis in TRAMP mice in association with increased cytotoxicity of natural killer cells",
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.",
author = "Singh, {Shivendra V.} and Renaud Warin and Dong Xiao and Powolny, {A. Anna} and Stan, {Silvia D.} and Arlotti, {Jlie A.} and Yan Zeng and Hahm, {Eun Ryeong} and Marynowski, {Stanley W.} and Ajay Bommareddy and Dhimant Desai and Shantu Amin and Parise, {Robert A.} and Beumer, {Jan H.} and Chambers, {William H.}",
year = "2009",
month = "3",
day = "1",
doi = "10.1158/0008-5472.CAN-08-3502",
language = "English (US)",
volume = "69",
pages = "2117--2125",
journal = "Cancer Research",
issn = "0008-5472",
number = "5",

}

Singh, SV, Warin, R, Xiao, D, Powolny, AA, Stan, SD, Arlotti, JA, Zeng, Y, Hahm, ER, Marynowski, SW, Bommareddy, A, Desai, D, Amin, S, Parise, RA, Beumer, JH & Chambers, WH 2009, 'Sulforaphane inhibits prostate carcinogenesis and pulmonary metastasis in TRAMP mice in association with increased cytotoxicity of natural killer cells', Cancer Research, vol. 69, no. 5, pp. 2117-2125. https://doi.org/10.1158/0008-5472.CAN-08-3502

Sulforaphane inhibits prostate carcinogenesis and pulmonary metastasis in TRAMP mice in association with increased cytotoxicity of natural killer cells. / Singh, Shivendra V.; Warin, Renaud; Xiao, Dong; Powolny, A. Anna; Stan, Silvia D.; Arlotti, Jlie A.; Zeng, Yan; Hahm, Eun Ryeong; Marynowski, Stanley W.; Bommareddy, Ajay; Desai, Dhimant; Amin, Shantu; Parise, Robert A.; Beumer, Jan H.; Chambers, William H.

In: Cancer Research, Vol. 69, No. 5, 01.03.2009, p. 2117-2125.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Sulforaphane inhibits prostate carcinogenesis and pulmonary metastasis in TRAMP mice in association with increased cytotoxicity of natural killer cells

AU - Singh, Shivendra V.

AU - Warin, Renaud

AU - Xiao, Dong

AU - Powolny, A. Anna

AU - Stan, Silvia D.

AU - Arlotti, Jlie A.

AU - Zeng, Yan

AU - Hahm, Eun Ryeong

AU - Marynowski, Stanley W.

AU - Bommareddy, Ajay

AU - Desai, Dhimant

AU - Amin, Shantu

AU - Parise, Robert A.

AU - Beumer, Jan H.

AU - Chambers, William H.

PY - 2009/3/1

Y1 - 2009/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=62449233418&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=62449233418&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-08-3502

DO - 10.1158/0008-5472.CAN-08-3502

M3 - Article

C2 - 19223537

AN - SCOPUS:62449233418

VL - 69

SP - 2117

EP - 2125

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 5

ER -