Chemopreventive effects of PBI-Se, a selenium-containing analog of PBIT, on AOM-induced aberrant crypt foci in F344 rats

Janakiram,Naveena   B.; Mohammed,Altaf; Ravillah,Durgadevi; Choi,Chang   In; Zhang,Yuting; Desai,Dhimant; Amin,Shantu; Rao,Chinthalapally  V.

doi:10.3892/or.2013.2483

Chemopreventive effects of PBI-Se, a selenium-containing analog of PBIT, on AOM-induced aberrant crypt foci in F344 rats

Authors:
- Naveena B. Janakiram
- Altaf Mohammed
- Durgadevi Ravillah
- Chang In Choi
- Yuting Zhang
- Dhimant Desai
- Shantu Amin
- Chinthalapally V. Rao
View Affiliations

Affiliations: Center for Cancer Prevention and Drug Development, Hematology/Oncology Section, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA, Department of Pharmacy, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
Published online on: May 23, 2013 https://doi.org/10.3892/or.2013.2483
Pages: 952-960

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Inducible nitric oxide synthase (iNOS) is a potential target for the treatment of inflammation and cancer. Previously, we showed that the selective iNOS inhibitor S,S'-1,4-phenylenebis(1,2-ethanediyl)bis-isothiourea (PBIT) caused significant inhibition of colon carcinogenesis induced by azoxymethane (AOM), although it did not completely abrogate NO production due to the exogenous bioavailability of NO and NO generation by eNOS in tumor tissues. To create an iNOS-targeting molecule that may have additional benefits, a novel isosteric analog of PBIT, PBI-Se, was developed, in which sulfur was replaced with selenium. Chemopreventive efficacy of PBI-Se was evaluated in an AOM-induced rat colon carcinogenesis model using aberrant crypt foci (ACF) as the endpoint. At 7 weeks of age, rats (12/group) were fed the control diet (AIN 76A) and then colonic ACF were induced with two AOM treatments. Three days later, rats were fed diets containing PBI-Se (0-20 ppm) for 8 weeks, and then ACF were evaluated histopathologically. Dietary administration of 10 or 20 ppm of PBI-Se significantly suppressed AOM-induced total colonic ACF formation (32 or 41%, p<0.002-0.0003), and multi-crypt (4 or more) aberrant foci (29 or 47%, p<0.01-0.0004), respectively. The inhibition by PBI-Se was dose-dependent and was half the dose of PBIT for inhibiting total ACF in rats. Both PBIT and PBI-Se induced dose-dependent apoptosis in CaCo2 cells and caused a significant decrease in the cell cycle proteins cyclin D1 (70%, p<0.0001) and iNOS (99%, p<0.0001). Treatment with PBIT (30 and 60 µM) and PBI-Se (2 and 4 µM) significantly decreased the LPS-induced cytokine interleukin-6 level. Incorporation of selenium into the structure of PBIT provided the agent with additional novel cytotoxic and immunologic properties. Results from the in vitro and in vivo bioassays suggest that PBI-Se could be developed further for the prevention and treatment of colon cancer.

View Figures

View References

1	American Cancer Society. Colorectal cancer key statistics. Available at: http://www.cancer.org/Cancer/ColonandRectumCancer/DetailedGuidecolorectal-cancer-key-statistics.
2	Jackson JR, Seed MP, Kircher CH, Willoughby DA and Winkler JD: The codependence of angiogenesis and chronic inflammation. FASEB J. 11:457–465. 1997.PubMed/NCBI
3	Phoa N and Epe B: Influence of nitric oxide on the generation and repair of oxidative DNA damage in mammalian cells. Carcinogenesis. 23:469–475. 2002. View Article : Google Scholar : PubMed/NCBI
4	Jaiswal M, LaRusso NF, Burgart LJ and Gores GJ: Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism. Cancer Res. 60:184–190. 2000.PubMed/NCBI
5	Moore MA: Cytokine and chemokine networks influencing stem cell proliferation, differentiation, and marrow homing. J Cell Biochem. 38:29–38. 2002. View Article : Google Scholar : PubMed/NCBI
6	Nakajima N, Kuwayama H, Ito Y, Iwasaki A and Arakawa Y: Helicobacter pylori, neutrophils, interleukins, and gastric epithelial proliferation. J Clin Gastroenterol. 25:S198–S202. 1997. View Article : Google Scholar
7	Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S and DuBois RN: Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology. 107:1183–1188. 1994.PubMed/NCBI
8	Rhodes JM and Campbell BJ: Inflammation and colorectal cancer: IBD-associated and sporadic cancer compared. Trends Mol Med. 8:10–16. 2002. View Article : Google Scholar : PubMed/NCBI
9	Keshavarzian A, Fusunyan RD, Jacyno M, Winship D, MacDermott RP and Sanderson IR: Increased interleukin-8 (IL-8) in rectal dialysate from patients with ulcerative colitis: evidence for a biological role for IL-8 in inflammation of the colon. Am J Gastroenterol. 94:704–712. 1999. View Article : Google Scholar : PubMed/NCBI
10	Nusrat A, Sitaraman SV and Neish A: Interaction of bacteria and bacterial toxins with intestinal epithelial cells. Curr Gastroenterol Rep. 3:392–398. 2001. View Article : Google Scholar : PubMed/NCBI
11	Weiss HA and Forman D: Aspirin, non-steroidal anti-inflammatory drugs and protection from colorectal cancer: a review of the epidemiological evidence. Scand J Gastroenterol. 220:137–141. 1996. View Article : Google Scholar : PubMed/NCBI
12	Jenkins DC, Charles IG, Thomsen LL, et al: Roles of nitric oxide in tumour growth. Proc Natl Acad Sci USA. 92:4392–4396. 1995. View Article : Google Scholar : PubMed/NCBI
13	Ambs S, Merriam WG, Bennett WP, et al: Frequent nitric oxide synthase-2 expression in human colon adenomas: implication for tumour angiogenesis and colon cancer progression. Cancer Res. 58:334–341. 1998.PubMed/NCBI
14	Jobin C, Haskill S, Mayer L, Panja A and Sartor RB: Evidence for altered regulation of I kappa B alpha degradation in human colonic cells. J Immunol. 158:226–234. 1997.PubMed/NCBI
15	Knowles RG and Moncada S: Nitric oxide synthases in mammals. Biochem J. 298:249–258. 1994.PubMed/NCBI
16	Forstermann U, Gath I, Schwarz P, Closs EI and Kleinert H: Isoforms of nitric oxide synthase. Properties, cellular distribution and expressional control. Biochem Pharmacol. 50:1321–1332. 1995. View Article : Google Scholar : PubMed/NCBI
17	Pana MH and Ho CT: Chemopreventive effects of natural dietary compounds on cancer development. Chem Soc Rev. 37:2558–2574. 2008. View Article : Google Scholar : PubMed/NCBI
18	Rao CV, Kawamori T, Hamid R and Reddy BS: Chemoprevention of colonic aberrant crypt foci by an inducible nitric oxide synthase-selective inhibitor. Carcinogenesis. 2:641–644. 1999.PubMed/NCBI
19	Briske-Anderson MJ, Finley JW and Newman SM: The influence of culture time and passage number on the morphological and physiological development of CaCo2 cells. Proc Soc Exp Biol Med. 214:248–257. 1997. View Article : Google Scholar : PubMed/NCBI
20	Huang Y, Li N, Liboni K and Neu J: Glutamine decreases lipopolysaccharide-induced IL-8 production in Caco-2 cells through a non-NF-kappaB p50 mechanism. Cytokine. 22:77–83. 2003. View Article : Google Scholar : PubMed/NCBI
21	Chittezhath M, Deep G, Singh RP, Agarwal C and Agarwal R: Silibinin inhibits cytokine-induced STATs, MAPKs, NF-κB and AP-1 activation, and down-regulates HIF-1α and iNOS in human lung carcinoma A549 cells. Mol Cancer Ther. 7:1817–1826. 2008.
22	Bird RP: Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: preliminary findings. Cancer Lett. 37:147–151. 1987. View Article : Google Scholar : PubMed/NCBI
23	Janakiram NB, Mohammed A, Zhang Y, Choi CI, Woodward C, Collin P, Steele VE and Rao CV: Chemopreventive effects of Frondanol A5, a Cucumaria frondosa extract, against rat colon carcinogenesis and inhibition of human colon cancer cell growth. Cancer Prev Res. 3:82–91. 2010.PubMed/NCBI
24	Arthur JR, McKenzie RC and Beckett GJ: Selenium in the immune system. J Nutr. 133:S1457–S1459. 2003.
25	Chung CY, Madhunapantula SV, Desai D, Amin S and Robertson GP: Melanoma prevention using topical PBI-Se. Cancer Prev Res. 4:935–948. 2011. View Article : Google Scholar : PubMed/NCBI
26	Vermeulen K, Van Bockstaele DR and Berneman ZN: The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 36:131–149. 2003. View Article : Google Scholar : PubMed/NCBI
27	Fusunyan RD, Quinn JJ, Fujimoto M, MacDermott RP and Sanderson IR: Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation. Mol Med. 5:631–640. 1999.PubMed/NCBI
28	Ogle CK, Guo XL, Hasselgren PO, Ogle JD and Alexander JW: The gut as a source of inflammatory cytokines after stimulation with endotoxin. Eur J Surg. 163:45–51. 1997.PubMed/NCBI
29	Haller D, Bode C, Hammes WP, Pfeifer AMA, Schiffrin EJ and Blum S: Non-pathogenic bacteria elicit a differential cytokine response by intestinal epithelial cell/leucocyte co-cultures. Gut. 47:79–87. 2000. View Article : Google Scholar : PubMed/NCBI
30	Kibriya MG, Jasmine F, Argos M, Verret WJ, Rakibuz-Zaman M, Ahmed A, Parvez F and Ahsan H: Changes in gene expression profiles in response to selenium supplementation among individuals with arsenic-induced pre-malignant skin lesions. Toxicol Lett. 169:162–176. 2007. View Article : Google Scholar : PubMed/NCBI
31	Terui Y, Ikeda M, Tomizuka H, et al: Identification of a novel apoptosis-inducing factor derived from leukemic cells: endothelial interleukin-8, but not monocyte-derived, induces apoptosis in leukemic cells. Biochem Biophys Res Commun. 243:407–411. 1998. View Article : Google Scholar
32	Terui Y, Ikeda M, Tomizuka H, et al: Activated endothelial cells induce apoptosis in leukemic cells by endothelial interleukin-8. Blood. 92:2672–2680. 1998.PubMed/NCBI
33	Hoffmann E, Dittrich-Breiholz O, Holtmann H and Kracht M: Multiple control of interleukin-8 gene expression. J Leukoc Biol. 72:847–855. 2002.PubMed/NCBI
34	Garat C and Arend WP: Intracellular IL-1Ra type 1 inhibits IL-1-induced IL-6 and IL-8 production in Caco-2 intestinal epithelial cells through inhibition of p38 mitogen-activated protein kinase and NF-kappaB pathways. Cytokine. 23:31–40. 2003. View Article : Google Scholar
35	Lee Li-F, Hellendall RP, Wang Y, Stephen Haskill J, Mukaida N, Matsushima K and Ting JP: IL-8 reduced tumorigenicity of human ovarian cancer in vivo due to neutrophil infiltration. J Immunol. 164:2769–2775. 2000. View Article : Google Scholar : PubMed/NCBI
36	Molica S, Vitelli G, Levato D, Levato L, Datillo A and Gandolfo GM: Clinico-biological implications of increased serum levels of interleukin −8 in B cell chronic lymphocytic leukemia. Haematologica. 84:208–211. 1999.PubMed/NCBI
37	Gartner R, Albrich W and Angstwurm MW: The effect of a selenium supplementation on the outcome of patients with severe systemic inflammation, burn, and trauma. Biofactors. 14:199–204. 2001. View Article : Google Scholar : PubMed/NCBI
38	Murata Y, Ishiguro Y, Itoh J, Munakata A and Yoshida Y: The role of pro-inflammatory and immunoregulatory cytokines in the pathogenesis of ulcerative colitis. Gastroenterol Clin North Am J. 30:56–60. 1995.
39	Combs GF Jr and Gray WP: Chemopreventive agents: selenium. Pharmacol Ther. 79:179–192. 1998. View Article : Google Scholar : PubMed/NCBI
40	Russo MW, Murray SC, Wurzelmann JI, Woosley JT and Sandler RS: Plasma selenium levels and the risk of colorectal adenomas. Nutr Cancer. 28:125–129. 1997. View Article : Google Scholar : PubMed/NCBI
41	Patterson BH and Levander OA: Naturally occurring selenium compounds in cancer chemoprevention trials: a workshop summary. Cancer Epidemiol Biomarkers Prev. 6:63–69. 1997.PubMed/NCBI
42	Knekt P, Marniemi J, Teppo L, Heliovaara M and Aromaa A: Is low selenium status a risk factor for lung cancer? Am J Epidemiol. 148:975–982. 1998. View Article : Google Scholar : PubMed/NCBI
43	Fleet JC: Dietary selenium repletion may reduce cancer incidence in people at high risk who live in areas with low soil selenium. Nutr Rev. 55:277–279. 1997. View Article : Google Scholar : PubMed/NCBI
44	Shamberger RJ: The genotoxicity of selenium. Mutat Res. 154:28–48. 1985.
45	Young KL and Lee PN: Intervention studies on cancer. Eur J Cancer Prev. 8:91–103. 1999. View Article : Google Scholar
46	Burguera JL, Burguera M, Gallignani M, Alarcon OM and Burgueera JA: Blood serum selenium in the province of Merida, Venezuela, related to sex, cancer incidence and soil selenium content. J Trace Elem Electrolytes Health Dis. 4:73–77. 1990.PubMed/NCBI
47	Combs GF Jr, Clark LC and Turnbull BW: Reduction of cancer risk with an oral supplement of selenium. Biomed Environ Sci. 10:227–234. 1997.PubMed/NCBI
48	Clark LC, Combs GF Jr, Turnbull BW, et al: Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. JAMA. 276:1957–1963. 1996. View Article : Google Scholar
49	Combs GF Jr, Clark LC and Turnbull BW: An analysis of cancer prevention by selenium. Biofactors. 14:153–159. 2001. View Article : Google Scholar : PubMed/NCBI
50	Combs GF Jr: Food system-based approaches to improving micronutrient nutrition: the case for selenium. Biofactors. 12:39–43. 2000. View Article : Google Scholar : PubMed/NCBI
51	Zimmerman MB and Kohrle J: The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health. Thyroid. 12:867–878. 2002. View Article : Google Scholar : PubMed/NCBI
52	Ryan-Harshman M and Aldoori W: The relevance of selenium to immunity, cancer and infectious/inflammatory diseases. Can J Diet Pract Res. 66:98–102. 2005. View Article : Google Scholar : PubMed/NCBI
53	Wood SM, Beckham C, Yosioka A, Darban H and Watson RR: Beta-carotene and selenium supplementation enhances immune response in aged humans. Integr Med. 2:85–92. 2000. View Article : Google Scholar : PubMed/NCBI
54	Baum MK, Miguez-Burbano MJ, Campa A and Shor-Posner G: Selenium and interleukins in persons infected with human immunodeficiency virus type 1. J Infect Dis. 182:S69–S73. 2000. View Article : Google Scholar : PubMed/NCBI
55	Lippman SM, Klein EA, Goodman PJ, et al: Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 301:39–51. 2009. View Article : Google Scholar : PubMed/NCBI
56	Whanger PD: Selenium and its relationship to cancer: an update. Br J Nutr. 91:11–28. 2004. View Article : Google Scholar : PubMed/NCBI