Carcinogenesis, Vol. 21, No. 12, 2287-2291,
December 2000
© 2000 Oxford University Press
SHORT COMMUNICATION |
Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate
1 Division of Carcinogenesis and Molecular Epidemiology and
2 Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla, NY 10595, USA
Epidemiological studies have linked consumption of broccoli to a reduced risk of colon cancer in individuals with the glutathione S-transferase M1 (GSTM1) null genotype. GSTs are involved in excretion and elimination of isothiocyanates (ITCs), which are major constituents of broccoli and other cruciferous vegetables and have cancer chemopreventive potential, so it is speculated that ITCs may play a role in protection against human colon cancer. However, there is a lack of data from animal studies to support this. We carried out a bioassay to examine whether sulforaphane (SFN) and phenethyl isothiocyanate (PEITC), major ITCs in broccoli and watercress, respectively, and their corresponding N-acetylcysteine (NAC) conjugates, show any chemopreventive activity towards azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in F344 rats. Groups of six male F344 rats were treated with AOM subcutaneously (15 mg/kg body wt) once weekly for 2 weeks. SFN and PEITC and their NAC conjugates were administered by gavage either three times weekly for 8 weeks (5 and 20 µmol, respectively) after AOM dosing (post-initiation stage) or once daily for 3 days (20 and 50 µmol, respectively) before AOM treatment (initiation stage). The bioassay was terminated on week 10 after the second AOM dosing and ACF were quantified. SFN, SFN-NAC, PEITC and PEITC-NAC all significantly reduced the formation of total ACF from 153 to 100–116 (P < 0.01) and multicrypt foci from 52 to 27–38 (more than four crypts/focus; P < 0.05) during the post-initiation treatment. However, only SFN and PEITC were effective during the initiation phase, reducing the total ACF from 153 to 109–115 (P < 0.01) and multicrypt foci from 52 to 35 (more than four crypts/focus; P < 0.05). The NAC conjugates were inactive as anti-initiators against AOM-induced ACF. These findings provide important laboratory evidence for a potential role of SFN and PEITC in the protection against colon cancer.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. A. Moy, J.-M. Yuan, F.-L. Chung, D. Van Den Berg, R. Wang, Y.-T. Gao, and M. C. Yu Urinary Total Isothiocyanates and Colorectal Cancer: A Prospective Study of Men in Shanghai, China Cancer Epidemiol. Biomarkers Prev., June 1, 2008; 17(6): 1354 - 1359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Munday, P. Mhawech-Fauceglia, C. M. Munday, J. D. Paonessa, L. Tang, J. S. Munday, C. Lister, P. Wilson, J. W. Fahey, W. Davis, et al. Inhibition of Urinary Bladder Carcinogenesis by Broccoli Sprouts Cancer Res., March 1, 2008; 68(5): 1593 - 1600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Pappa, J. Strathmann, M. Lowinger, H. Bartsch, and C. Gerhauser Quantitative combination effects between sulforaphane and 3,3'-diindolylmethane on proliferation of human colon cancer cells in vitro Carcinogenesis, July 1, 2007; 28(7): 1471 - 1477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Aleksunes and J. E. Manautou Emerging Role of Nrf2 in Protecting Against Hepatic and Gastrointestinal Disease Toxicol Pathol, June 1, 2007; 35(4): 459 - 473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Herman-Antosiewicz, H. Xiao, K. L. Lew, and S. V. Singh Induction of p21 protein protects against sulforaphane-induced mitotic arrest in LNCaP human prostate cancer cell line Mol. Cancer Ther., May 1, 2007; 6(5): 1673 - 1681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Pledgie-Tracy, M. D. Sobolewski, and N. E. Davidson Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines Mol. Cancer Ther., March 1, 2007; 6(3): 1013 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Myzak, P. Tong, W.-M. Dashwood, R. H. Dashwood, and E. Ho Sulforaphane Retards the Growth of Human PC-3 Xenografts and Inhibits HDAC Activity in Human Subjects Experimental Biology and Medicine, February 1, 2007; 232(2): 227 - 234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Choi, K. L. Lew, H. Xiao, A. Herman-Antosiewicz, D. Xiao, C. K. Brown, and S. V. Singh D,L-Sulforaphane-induced cell death in human prostate cancer cells is regulated by inhibitor of apoptosis family proteins and Apaf-1 Carcinogenesis, January 1, 2007; 28(1): 151 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zhou, E.-J. Poulton, F. Grun, T. K. Bammler, B. Blumberg, K. E. Thummel, and D. L. Eaton The Dietary Isothiocyanate Sulforaphane Is an Antagonist of the Human Steroid and Xenobiotic Nuclear Receptor Mol. Pharmacol., January 1, 2007; 71(1): 220 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xiao, K. L. Lew, Y. Zeng, H. Xiao, S. W. Marynowski, R. Dhir, and S. V. Singh Phenethyl isothiocyanate-induced apoptosis in PC-3 human prostate cancer cells is mediated by reactive oxygen species-dependent disruption of the mitochondrial membrane potential Carcinogenesis, November 1, 2006; 27(11): 2223 - 2234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Zhang, S. Loganathan, I. Humphreys, and S. K. Srivastava Benzyl Isothiocyanate-Induced DNA Damage Causes G2/M Cell Cycle Arrest and Apoptosis in Human Pancreatic Cancer Cells J. Nutr., November 1, 2006; 136(11): 2728 - 2734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Hu, T. O. Khor, G. Shen, W.-S. Jeong, V. Hebbar, C. Chen, C. Xu, B. Reddy, K. Chada, and A.-N. T. Kong Cancer chemoprevention of intestinal polyposis in ApcMin/+ mice by sulforaphane, a natural product derived from cruciferous vegetable Carcinogenesis, October 1, 2006; 27(10): 2038 - 2046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-a. Matsui, Y. Sowa, T. Yoshida, H. Murata, M. Horinaka, M. Wakada, R. Nakanishi, T. Sakabe, T. Kubo, and T. Sakai Sulforaphane enhances TRAIL-induced apoptosis through the induction of DR5 expression in human osteosarcoma cells Carcinogenesis, September 1, 2006; 27(9): 1768 - 1777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Xu, M.-T. Huang, G. Shen, X. Yuan, W. Lin, T. O. Khor, A. H. Conney, and A.-N. T. Kong Inhibition of 7,12-Dimethylbenz(a)anthracene-Induced Skin Tumorigenesis in C57BL/6 Mice by Sulforaphane Is Mediated by Nuclear Factor E2-Related Factor 2 Cancer Res., August 15, 2006; 66(16): 8293 - 8296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Xu, X. Yuan, Z. Pan, G. Shen, J.-H. Kim, S. Yu, T. O. Khor, W. Li, J. Ma, and A.-N. T. Kong Mechanism of action of isothiocyanates: the induction of ARE-regulated genes is associated with activation of ERK and JNK and the phosphorylation and nuclear translocation of Nrf2. Mol. Cancer Ther., August 1, 2006; 5(8): 1918 - 1926. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Herman-Antosiewicz, D. E. Johnson, and S. V. Singh Sulforaphane Causes Autophagy to Inhibit Release of Cytochrome c and Apoptosis in Human Prostate Cancer Cells Cancer Res., June 1, 2006; 66(11): 5828 - 5835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Myzak, K. Hardin, R. Wang, R. H. Dashwood, and E. Ho Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP and PC-3 prostate epithelial cells Carcinogenesis, April 1, 2006; 27(4): 811 - 819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bertl, H. Bartsch, and C. Gerhauser Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention. Mol. Cancer Ther., March 1, 2006; 5(3): 575 - 585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Xu, G. Shen, X. Yuan, J.-h. Kim, A. Gopalkrishnan, Y.-S. Keum, S. Nair, and A.-N. T. Kong ERK and JNK signaling pathways are involved in the regulation of activator protein 1 and cell death elicited by three isothiocyanates in human prostate cancer PC-3 cells Carcinogenesis, March 1, 2006; 27(3): 437 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Y.A. Plate and D. D. Gallaher Effects of Indole-3-Carbinol and phenethyl isothiocyanate on colon carcinogenesis induced by azoxymethane in rats Carcinogenesis, February 1, 2006; 27(2): 287 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-M. Yang, M. Jhanwar-Uniyal, J. Schwartz, C. C. Conaway, H. D. Halicka, F. Traganos, and F.-L. Chung N-Acetylcysteine Conjugate of Phenethyl Isothiocyanate Enhances Apoptosis in Growth-Stimulated Human Lung Cells Cancer Res., September 15, 2005; 65(18): 8538 - 8547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Conaway, C.-X. Wang, B. Pittman, Y.-M. Yang, J. E. Schwartz, D. Tian, E. J. McIntee, S. S. Hecht, and F.-L. Chung Phenethyl Isothiocyanate and Sulforaphane and their N-Acetylcysteine Conjugates Inhibit Malignant Progression of Lung Adenomas Induced by Tobacco Carcinogens in A/J Mice Cancer Res., September 15, 2005; 65(18): 8548 - 8557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V. Singh, S. K. Srivastava, S. Choi, K. L. Lew, J. Antosiewicz, D. Xiao, Y. Zeng, S. C. Watkins, C. S. Johnson, D. L. Trump, et al. Sulforaphane-induced Cell Death in Human Prostate Cancer Cells Is Initiated by Reactive Oxygen Species J. Biol. Chem., May 20, 2005; 280(20): 19911 - 19924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Choi and S. V. Singh Bax and Bak Are Required for Apoptosis Induction by Sulforaphane, a Cruciferous Vegetable-Derived Cancer Chemopreventive Agent Cancer Res., March 1, 2005; 65(5): 2035 - 2043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N.-A. Pham, J. W. Jacobberger, A. D. Schimmer, P. Cao, M. Gronda, and D. W. Hedley The dietary isothiocyanate sulforaphane targets pathways of apoptosis, cell cycle arrest, and oxidative stress in human pancreatic cancer cells and inhibits tumor growth in severe combined immunodeficient mice Mol. Cancer Ther., October 1, 2004; 3(10): 1239 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Srivastava and S. V. Singh Cell cycle arrest, apoptosis induction and inhibition of nuclear factor kappa B activation in anti-proliferative activity of benzyl isothiocyanate against human pancreatic cancer cells Carcinogenesis, September 1, 2004; 25(9): 1701 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Myzak, P. A. Karplus, F.-L. Chung, and R. H. Dashwood A Novel Mechanism of Chemoprotection by Sulforaphane: Inhibition of Histone Deacetylase Cancer Res., August 15, 2004; 64(16): 5767 - 5774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Smith, E. K. Lund, M. L. Parker, R. G. Clarke, and I. T. Johnson Allyl-isothiocyanate causes mitotic block, loss of cell adhesion and disrupted cytoskeletal structure in HT29 cells Carcinogenesis, August 1, 2004; 25(8): 1409 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Tang and Y. Zhang Dietary Isothiocyanates Inhibit the Growth of Human Bladder Carcinoma Cells J. Nutr., August 1, 2004; 134(8): 2004 - 2010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Hu, V. Hebbar, B.-R. Kim, C. Chen, B. Winnik, B. Buckley, P. Soteropoulos, P. Tolias, R. P. Hart, and A.-N. T. Kong In Vivo Pharmacokinetics and Regulation of Gene Expression Profiles by Isothiocyanate Sulforaphane in the Rat J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 263 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhang and G. B. Gordon A strategy for cancer prevention: Stimulation of the Nrf2-ARE signaling pathway Mol. Cancer Ther., July 1, 2004; 3(7): 885 - 893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. V. Singh, A. Herman-Antosiewicz, A. V. Singh, K. L. Lew, S. K. Srivastava, R. Kamath, K. D. Brown, L. Zhang, and R. Baskaran Sulforaphane-induced G2/M Phase Cell Cycle Arrest Involves Checkpoint Kinase 2-mediated Phosphorylation of Cell Division Cycle 25C J. Biol. Chem., June 11, 2004; 279(24): 25813 - 25822. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-S. Keck and J. W. Finley Cruciferous Vegetables: Cancer Protective Mechanisms of Glucosinolate Hydrolysis Products and Selenium Integr Cancer Ther, March 1, 2004; 3(1): 5 - 12. [Abstract] [PDF]
|
|
|
|
|
|
A. V. Singh, D. Xiao, K. L. Lew, R. Dhir, and S. V. Singh Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo Carcinogenesis, January 1, 2004; 25(1): 83 - 90. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-R. Kim, R. Hu, Y.-S. Keum, V. Hebbar, G. Shen, S. S. Nair, and A-N. T. Kong Effects of Glutathione on Antioxidant Response Element-Mediated Gene Expression and Apoptosis Elicited by Sulforaphane Cancer Res., November 1, 2003; 63(21): 7520 - 7525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Srivastava, D. Xiao, K. L. Lew, P. Hershberger, D. M. Kokkinakis, C. S. Johnson, D. L. Trump, and S. V. Singh Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits growth of PC-3 human prostate cancer xenografts in vivo Carcinogenesis, October 1, 2003; 24(10): 1665 - 1670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xiao, S. K. Srivastava, K. L. Lew, Y. Zeng, P. Hershberger, C. S. Johnson, D. L. Trump, and S. V. Singh Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits proliferation of human prostate cancer cells by causing G2/M arrest and inducing apoptosis Carcinogenesis, May 1, 2003; 24(5): 891 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Seow, J.-M. Yuan, C.-L. Sun, D. Van Den Berg, H.-P. Lee, and M. C. Yu Dietary isothiocyanates, glutathione S-transferase polymorphisms and colorectal cancer risk in the Singapore Chinese Health Study Carcinogenesis, December 1, 2002; 23(12): 2055 - 2061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Thimmulappa, K. H. Mai, S. Srisuma, T. W. Kensler, M. Yamamoto, and S. Biswal Identification of Nrf2-regulated Genes Induced by the Chemopreventive Agent Sulforaphane by Oligonucleotide Microarray Cancer Res., September 15, 2002; 62(18): 5196 - 5203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Kassie, S. Rabot, M. Uhl, W. Huber, H. M. Qin, C. Helma, R. Schulte-Hermann, and S. Knasmuller Chemoprotective effects of garden cress (Lepidium sativum) and its constituents towards 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ)-induced genotoxic effects and colonic preneoplastic lesions Carcinogenesis, July 1, 2002; 23(7): 1155 - 1161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xiao and S. V. Singh Phenethyl Isothiocyanate-induced Apoptosis in p53-deficient PC-3 Human Prostate Cancer Cell Line Is Mediated by Extracellular Signal-regulated Kinases Cancer Res., July 1, 2002; 62(13): 3615 - 3619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Fahey, X. Haristoy, P. M. Dolan, T. W. Kensler, I. Scholtus, K. K. Stephenson, P. Talalay, and A. Lozniewski Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors PNAS, May 28, 2002; 99(11): 7610 - 7615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-M. Yang, C. C. Conaway, J. W. Chiao, C.-X. Wang, S. Amin, J. Whysner, W. Dai, J. Reinhardt, and F.-L. Chung Inhibition of Benzo(a)pyrene-induced Lung Tumorigenesis in A/J Mice by Dietary N-Acetylcysteine Conjugates of Benzyl and Phenethyl Isothiocyanates during the Postinitiation Phase Is Associated with Activation of Mitogen-activated Protein Kinases and p53 Activity and Induction of Apoptosis Cancer Res., January 1, 2002; 62(1): 2 - 7. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Heiss, C. Herhaus, K. Klimo, H. Bartsch, and C. Gerhauser Nuclear Factor kappa B Is a Molecular Target for Sulforaphane-mediated Anti-inflammatory Mechanisms J. Biol. Chem., August 17, 2001; 276(34): 32008 - 32015. [Abstract] [Full Text] [PDF]
|
|