Inhibition of androgen-responsive LNCaP prostate cancer cell tumor xenograft growth by dietary phenethyl isothiocyanate correlates with decreased angiogenesis and inhibition of cell attachment

Hudson,Tamaro   S.; Perkins,Susan N.; Hursting,Stephen  D.; Young,Heather   A.; Kim,Young  S.; Wang,Tien-Chung; Wang,Thomas  T.Y.

doi:10.3892/ijo.2012.1335

Inhibition of androgen-responsive LNCaP prostate cancer cell tumor xenograft growth by dietary phenethyl isothiocyanate correlates with decreased angiogenesis and inhibition of cell attachment

Authors:
- Tamaro S. Hudson
- Susan N. Perkins
- Stephen D. Hursting
- Heather A. Young
- Young S. Kim
- Tien-Chung Wang
- Thomas T.Y. Wang
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Affiliations: Laboratory of Cellular Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, Genomics and Immunology Laboratory, Beltsville Human Nutrition Research Center, ARS, USDA, 1300 Baltimore Avenue Building 307C, Room 132, Beltsville, MD 20705, USA
Published online on: January 17, 2012 https://doi.org/10.3892/ijo.2012.1335
Pages: 1113-1121

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Abstract

Phenethyl isothiocyanate (PEITC) is a candidate anticancer compound found in certain cruciferous vegetables. In our tumor cell xenograft model, dietary administration of PEITC (100-150 mg/kg body weight/d) inhibited androgen-responsive LNCaP human prostate cancer cell tumor growth. We found that dietary treatment with PEITC significantly inhibited tumor platelet/endothelial cell adhesion molecule (PECAM-1/CD31) expression, a marker of angiogenesis. By contrast, we did not find the inhibitory effects of PEITC on tumor growth to be associated with alteration of specific markers for apoptosis, cell proliferation or androgen receptor-mediated pathways. Consistent with in vivo results, PEITC exerted little effects on cell proliferation, cell cycle and androgen-dependent pathways. Interestingly, PEITC significantly attenuated LNCaP cell plating efficiency that correlated with inhibition of integrin family proteins integrin β1, α2 and α6 mRNA expression. Thus, PEITC may be a dietary factor that inhibits androgen-responsive prostate tumor growth indirectly by selectively targeting factors involved in the tumor microenvironment.

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1	Ozasa K, Nakao M, Watanabe Y, Hayashi K, et al: Serum phyto-estrogens and prostate cancer risk in a nested case-control study among Japanese men. Cancer Sci. 95:65–71. 2004. View Article : Google Scholar : PubMed/NCBI
2	Boyle P, Levi F, Lucchini F, La Vecchia C, et al: Trends in diet-related cancers in Japan: a conundrum? Lancet. 342:7521993. View Article : Google Scholar : PubMed/NCBI
3	Morton MS, Griffiths K and Blacklock N: The preventive role of diet in prostatic disease. Br J Urol. 77:481–493. 1996. View Article : Google Scholar : PubMed/NCBI
4	Cook LS, Goldoft M, Schwartz SM and Weiss NS: Incidence of adenocarcinoma of the prostate in Asian immigrants to the United States and their descendants. J Urol. 161:152–155. 1999. View Article : Google Scholar : PubMed/NCBI
5	Stellman SD and Wang QS: Cancer mortality in Chinese immigrants to New York City. Comparison with Chinese in Tianjin and with United States-born whites. Cancer. 73:1270–1275. 1994. View Article : Google Scholar : PubMed/NCBI
6	Schuman LM and Mandel JS: Epidemiology of prostatic cancer in blacks. Prev Med. 9:630–649. 1980. View Article : Google Scholar : PubMed/NCBI
7	Whittemore AS, Lele C, Friedman GD, Stamey T, et al: Prostate-specific antigen as predictor of prostate cancer in black men and white men. J Natl Cancer Inst. 87:354–360. 1995. View Article : Google Scholar : PubMed/NCBI
8	Singh RP and Agarwal R: Tumor angiogenesis: a potential target in cancer control by phytochemicals. Curr Cancer Drug Targets. 3:205–217. 2003. View Article : Google Scholar : PubMed/NCBI
9	Zarkovic N, Vukovic T, Loncaric I, Miletic M, et al: An overview on anticancer activities of the Viscum album extract Isorel. Cancer Biother Radiopharm. 16:55–62. 2001. View Article : Google Scholar : PubMed/NCBI
10	Hecht SS: Chemoprevention by isothiocyanates. J Cell Biochem. 22(Suppl): 195–209. 1995. View Article : Google Scholar
11	Zhang Y, Kensler TW, Cho CG, Posner GH and Talalay P: Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc Natl Acad Sci USA. 91:3147–3150. 1994. View Article : Google Scholar : PubMed/NCBI
12	Yu R, Mandlekar S, Harvey KJ, Ucker DS and Kong AN: Chemo-preventive isothiocyanates induce apoptosis and caspase-3-like protease activity. Cancer Res. 58:402–408. 1998.PubMed/NCBI
13	Xu K and Thornalley PJ: Involvement of glutathione metabolism in the cytotoxicity of the phenethyl isothiocyanate and its cysteine conjugate to human leukaemia cells in vitro. Biochem Pharmacol. 61:165–177. 2001. View Article : Google Scholar : PubMed/NCBI
14	Xiao D and Singh SV: Phenethyl isothiocyanate-induced apoptosis in p53-deficient PC-3 human prostate cancer cell line is mediated by extracellular signal-regulated kinases. Cancer Res. 62:3615–3619. 2002.PubMed/NCBI
15	Xu C, Shen G, Chen C, Gelinas C and Kong AN: Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells. Oncogene. 24:4486–4495. 2005. View Article : Google Scholar : PubMed/NCBI
16	Xiao D and Singh SV: Phenethyl isothiocyanate inhibits angiogenesis in vitro and ex vivo. Cancer Res. 67:2239–2246. 2007. View Article : Google Scholar : PubMed/NCBI
17	Morse MA, Reinhardt JC, Amin SG, Hecht SS, et al: Effect of dietary aromatic isothiocyanates fed subsequent to the administration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone on lung tumorigenicity in mice. Cancer Lett. 49:225–230. 1990. View Article : Google Scholar : PubMed/NCBI
18	Zhou JR, Gugger ET, Tanaka T, Guo Y, et al: Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice. J Nutr. 129:628–1635. 1999.PubMed/NCBI
19	Wang TT, Hudson TS, Wang TC, Remsberg CM, et al: Differential effects of resveratrol on androgen-responsive LNCaP human prostate cancer cells in vitro and in vivo. Carcinogenesis. 29:2001–2010. 2008. View Article : Google Scholar : PubMed/NCBI
20	Hunter AL, Choy JC and Granville DJ: Detection of apoptosis in cardiovascular diseases. Methods Mol Med. 112:277–289. 2005.PubMed/NCBI
21	Cher ML, Chew K, Rosenau W and Carroll PR: Cellular proliferation in prostatic adenocarcinoma as assessed by bromodeoxyuridine uptake and Ki-67 and PCNA expression. Prostate. 26:87–93. 1995. View Article : Google Scholar : PubMed/NCBI
22	Takahashi Y, Lavigne JA, Hursting SD, Chandramouli GV, et al: Molecular signatures of soy-derived phytochemicals in androgen-responsive prostate cancer cells: a comparison study using DNA microarray. Mol Carcinog. 45:943–956. 2006. View Article : Google Scholar : PubMed/NCBI
23	Goel HL, Alam N, Johnson IN and Languino LR: Integrin signaling aberrations in prostate cancer. Am J Transl Res. 1:211–220. 2009.PubMed/NCBI
24	Kim JH, Xu C, Keum YS, Reddy B, et al: Inhibition of EGFR signaling in human prostate cancer PC-3 cells by combination treatment with beta-phenylethyl isothiocyanate and curcumin. Carcinogenesis. 27:475–482. 2006. View Article : Google Scholar : PubMed/NCBI
25	Xiao D, Johnson CS, Trump DL and Singh SV: Proteasome-mediated degradation of cell division cycle 25C and cyclin-dependent kinase 1 in phenethyl isothiocyanate-induced G2-M-phase cell cycle arrest in PC-3 human prostate cancer cells. Mol Cancer Ther. 3:567–575. 2004.
26	Chen YR, Han J, Kori R, Kong AN and Tan TH: Phenylethyl isothiocyanate induces apoptotic signaling via suppressing phosphatase activity against c-Jun N-terminal kinase. J Biol Chem. 277:39334–39342. 2002. View Article : Google Scholar
27	Xiao D, Herman-Antosiewicz A, Antosiewicz J, Xiao H, et al: Diallyl trisulfide-induced G(2)-M phase cell cycle arrest in human prostate cancer cells is caused by reactive oxygen species-dependent destruction and hyperphosphorylation of Cdc 25 C. Oncogene. 24:6256–6268. 2005. View Article : Google Scholar
28	Van Moorselaar RJ and Voest EE: Angiogenesis in prostate cancer: its role in disease progression and possible therapeutic approaches. Mol Cell Endocrinol. 197:239–250. 2002.PubMed/NCBI
29	Weidner N, Carroll PR, Flax J, Blumenfeld W and Folkman J: Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol. 143:401–409. 1993.PubMed/NCBI
30	Cao G, O'Brien CD, Zhou Z, Sanders SM, et al: Involvement of human PECAM-1 in angiogenesis and in vitro endothelial cell migration. Am J Physiol Cell Physiol. 282:C1181–C1190. 2002. View Article : Google Scholar : PubMed/NCBI
31	Zeng ZZ, Jia Y, Hahn NJ, Markwart SM, Rockwood KF and Livant DL: Role of focal adhesion kinase and phosphatidylinositol 3′-kinase in integrin fibronectin receptor-mediated, matrix metalloproteinase-1-dependent invasion by metastatic prostate cancer cells. Cancer Res. 66:8091–8099. 2006.
32	Hall CL, Dubyk CW, Riesenberger TA, Shein D, Keller ET and van Golen KL: Type I collagen receptor (alpha2beta1) signaling promotes prostate cancer invasion through RhoC GTPase. Neoplasia. 10:797–803. 2008.PubMed/NCBI
33	Sroka IC, Anderson TA, McDaniel KM, Nagle RB, Gretzer MB and Cress AE: The laminin binding integrin alpha6beta1 in prostate cancer perineural invasion. J Cell Physiol. 224:283–288. 2010. View Article : Google Scholar : PubMed/NCBI
34	Morse MA, Zu H, Galati AJ, Schmidt CJ and Stoner GD: Dose-related inhibition by dietary phenethyl isothiocyanate of esophageal tumorigenesis and DNA methylation induced by N-nitrosomethylbenzylamine in rats. Cancer Lett. 72:103–110. 1993. View Article : Google Scholar : PubMed/NCBI
35	Stoner GD, Morrissey DT, Heur YH, Daniel EM, et al: Inhibitory effects of phenethyl isothiocyanate on N-nitrosobenzylmethylamine carcinogenesis in the rat esophagus. Cancer Res. 51:2063–2068. 1991.PubMed/NCBI
36	Wattenberg LW: Inhibition of carcinogen-induced neoplasia by sodium cyanate, tert-butyl isocyanate, and benzyl isothiocyanate administered subsequent to carcinogen exposure. Cancer Res. 41:2991–2994. 1981.
37	Wattenberg LW: Inhibitory effects of benzyl isothiocyanate administered shortly before diethylnitrosamine or benzo[a]pyrene on pulmonary and forestomach neoplasia in A/J mice. Carcinogenesis. 8:1971–1973. 1987.
38	Hsu JC, Zhang J, Dev A, Wing A, et al: Indole-3-carbinol inhibition of androgen receptor expression and downregulation of androgen responsiveness in human prostate cancer cells. Carcinogenesis. 26:1896–1904. 2005. View Article : Google Scholar : PubMed/NCBI
39	Talalay P and Fahey JW: Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism. J Nutr. 131:S3027–S3033. 2001.PubMed/NCBI