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Glycine- and proline-rich glycoprotein regulates the balance between cell proliferation and apoptosis for ACF formation in 1,2-dimethylhydrazine-treated A/J mice

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Abstract

The objective of this study was to investigate the chemopreventive potentials of glycine- and proline-rich glycoprotein (SNL glycoprotein, 150-kDa) isolated from Solanum nigrum Linne on formation of colonic aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH, 20 mg/kg) in A/J mice. Administration of SNL glycoprotein inhibited phosphorylation of extracellular signal-regulated kinase (ERK), expression of colonic proliferating cell nuclear antigen (PCNA), and frequency of colonic ACF in DMH-stimulated mice colon carcinogenesis. In addition, SNL glycoprotein increased expression of cyclin-dependent kinase inhibitors (p21WAF/Cip1 and p27Kip1), whereas reduced expression of precursor form of apoptosis-related proteins [pro-caspase-3 and pro-poly(ADP-ribose)polymerase (PARP)] in the mice. Interestingly, the results in this study revealed that SNL glycoprotein has suppressive effects on activity of nuclear factor-kappa B (NF-κB), whereas it has stimulatory effect on the expression of p53, accompanying inhibitory effects on expression of NF-κBp50, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, and tumor necrosis factor (TNF)-α in DMH-stimulated ACF formation. Also, SNL glycoprotein has inhibitory effects on the formation of thiobarbituric acid reactive substances (TBARS), on the production of inducible nitric oxide (NO), and on the release of lactate dehydrogenase (LDH) in the mice plasma. Collectively, our findings in this study suggest that SNL glycoprotein has chemopreventive activity via modulation of cell proliferation and apoptosis in DMH-treated A/J mice.

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References

  1. Greenwald P, Kelloff GJ, Boone CW, McDonald SS (1995) Genetic and cellular changes in colorectal cancer: proposed targets of chemopreventive agents. Cancer Epidemiol Biomarkers Prev 4:691–702

    PubMed  CAS  Google Scholar 

  2. Sharma RA, Manson MM, Gescher A, Steward WP (2001) Colorectal cancer chemoprevention: biochemical targets and clinical development of promising agents. Eur J Cancer 37:12–22. doi:10.1016/S0959-8049(00)00326-9

    Article  PubMed  CAS  Google Scholar 

  3. Mori H, Sugie S, Yoshimi N, Hara A, Tanaka T (1999) Control of cell proliferation in cancer prevention. Mutat Res 428:291–298. doi:10.1016/S1383-5742(99)00055-1

    PubMed  CAS  Google Scholar 

  4. Aranha MM, Borralho PM, Ravasco P, Moreira da Silva IB, Correia L, Fernandes A, Camilo ME, Rodrigues CM (2007) NF-kappaB and apoptosis in colorectal tumourigenesis. Eur J Clin Invest 37:416–424. doi:10.1111/j.1365-2362.2007.01801.x

    Article  PubMed  CAS  Google Scholar 

  5. Leonard SS, Harris GK, Shi X (2004) Metal-induced oxidative stress and signal transduction. Free Radic Biol Med 37:1921–1942. doi:10.1016/j.freeradbiomed.2004.09.010

    Article  PubMed  CAS  Google Scholar 

  6. Haupt S, Berger M, Goldberg Z, Haupt Y (2003) Apoptosis—the p53 network. J Cell Sci 116:4077–4085. doi:10.1242/jcs.00739

    Article  PubMed  CAS  Google Scholar 

  7. Ma Q, Hoper M, Anderson N, Rowlands BJ (1996) Effect of supplemental l-arginine in a chemical-induced model of colorectal cancer. World J Surg 20:1087–1091. doi:10.1007/s002689900165

    Article  PubMed  CAS  Google Scholar 

  8. McLellan EA, Bird RP (1988) Aberrant crypts: potential preneoplastic lesions in the murine colon. Cancer Res 48:6187–6192

    PubMed  CAS  Google Scholar 

  9. Shpitz B, Hay K, Medline A, Bruce WR, Vivona A, Gallinger S, Bull S, Stern N (1993) Aberrant crypt foci: early markers of malignancy in rat colon carcinogenesis. Proc Am Assoc Cancer Res 34:A684

    Google Scholar 

  10. Ooi VE, Liu F (2000) Immunomodulation and anti-cancer activity of polysaccharide–protein complexes. Curr Med Chem 7:715–729

    PubMed  CAS  Google Scholar 

  11. Lee SJ, Oh PS, Ko JH, Lim K, Lim KT (2004) A 150-kDa glycoprotein isolated from Solanum nigrum L. has cytotoxic and apoptotic effects by inhibiting the effects of protein kinase C alpha, nuclear factor-kappa B and inducible nitric oxide in HCT-116 cells. Cancer Chemother Pharmacol 54:562–572. doi:10.1007/s00280-004-0850-x

    Article  PubMed  CAS  Google Scholar 

  12. Lee SJ, Lim KT (2006) 150 kDa glycoprotein isolated from Solanum nigrum Linne stimulates caspase-3 activation and reduces inducible nitric oxide production in HCT-116 cells. Toxicol In Vitro 20:1088–1097. doi:10.1016/j.tiv.2006.01.019

    Article  PubMed  CAS  Google Scholar 

  13. Lim KT, Heo KS, Son YO (2002) Antioxidative and antimicrobial effects of glycoprotein isolated from Solanum nigrum Linne. Food Sci Biotechnol 11:484–489

    CAS  Google Scholar 

  14. Lee SJ, Lim KT (2003) Antioxidative effects of glycoprotein isolated from Solanum nigrum Linne on oxygen radicals and its cytotoxic effects on the MCF-7 cells. J Food Sci 68:466–470. doi:10.1111/j.1365-2621.2003.tb05695.x

    Article  CAS  Google Scholar 

  15. Bird RP (1987) Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: preliminary findings. Cancer Lett 37:147–151. doi:10.1016/0304-3835(87)90157-1

    Article  PubMed  CAS  Google Scholar 

  16. Bird RP, Good CK (2000) The significance of aberrant crypt foci in understanding the pathogenesis of colon cancer. Toxicol Lett 112–113:395–402. doi:10.1016/S0378-4274(99)00261-1

    Article  PubMed  Google Scholar 

  17. Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310. doi:10.1016/S0076-6879(78)52032-6

    Article  PubMed  CAS  Google Scholar 

  18. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 126:131–138. doi:10.1016/0003-2697(82)90118-X

    Article  PubMed  CAS  Google Scholar 

  19. Bergmeyer HU, Bernt E (1974) Lactate dehydrogenase. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp 574–579

    Google Scholar 

  20. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  21. Lee BM, Park KK (2003) Beneficial and adverse effects of chemopreventive agents. Mutat Res 523–524:265–278. doi:10.1016/S0027-5107(02)00342-1

    PubMed  Google Scholar 

  22. Sengupta A, Ghosh S, Das RK, Bhattacharjee S, Bhattacharya S (2006) Chemopreventive potential of diallylsulfide, lycopene and theaflavin during chemically induced colon carcinogenesis in rat colon through modulation of cyclooxygenase-2 and inducible nitric oxide synthase pathways. Eur J Cancer Prev 15:301–305. doi:10.1097/00008469-200608000-00005

    Article  PubMed  CAS  Google Scholar 

  23. Ferguson LR, Harris PJ (1999) Protection against cancer by wheat bran: role of dietary fibre and phytochemicals. Eur J Cancer Prev 8:17–25. doi:10.1097/00008469-199902000-00003

    Article  PubMed  CAS  Google Scholar 

  24. Johnstone SA, Gelmon K, Mayer LD, Hancock RE, Bally MB (2000) In vitro characterization of the anticancer activity of membrane-active cationic peptides. I. Peptide-mediated cytotoxicity and peptide-enhanced cytotoxic activity of doxorubicin against wild-type and p-glycoprotein over-expressing tumor cell lines. Anticancer Drug Des 15:151–160

    PubMed  CAS  Google Scholar 

  25. Zhang WM, Lai ZS, He MR, Xu G, Huang W, Zhou DY (2003) Effects of the antibacterial peptide cecropins from Chinese oak silkworm, Antheraea pernyi on 1,2-dimethylhydrazine-induced colon carcinogenesis in rats. Di Yi Jun Yi Da Xue Xue Bao 23:1066–1068

    PubMed  CAS  Google Scholar 

  26. Otvos L Jr (2000) Antibacterial peptides isolated from insects. J Pept Sci 6:497–511. doi:10.1002/1099-1387(200010)6:10<497::AID-PSC277>3.0.CO;2-W

    Article  PubMed  CAS  Google Scholar 

  27. Shin DM, Voravud N, Ro JY, Lee JS, Hong WK, Hittelman WN (1993) Sequential increases in proliferating cell nuclear antigen expression in head and neck tumorigenesis: a potential biomarker. J Natl Cancer Inst 85:971–978. doi:10.1093/jnci/85.12.971

    Article  PubMed  CAS  Google Scholar 

  28. Licato LL, Keku TO, Wurzelmann JI, Murray SC, Woosley JT, Sandler RS, Brenner DA (1997) In vivo activation of mitogen-activated protein kinases in rat intestinal neoplasia. Gastroenterology 113:1589–1598. doi:10.1053/gast.1997.v113.pm9352861

    Article  PubMed  CAS  Google Scholar 

  29. Widmann C, Gibson S, Jarpe MB, Johnson GL (1999) Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 79:143–180

    PubMed  CAS  Google Scholar 

  30. Kyriakis JM, Avruch J (2001) Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 81:807–869

    PubMed  CAS  Google Scholar 

  31. D’Abaco GM, Hooper S, Paterson H, Marshall CJ (2002) Loss of Rb overrides the requirement for ERK activity for cell proliferation. J Cell Sci 115:4607–4616. doi:10.1242/jcs.00161

    Article  PubMed  CAS  Google Scholar 

  32. Park KS, Ahn Y, Kim JA, Yun MS, Seong BL, Choi KY (2002) Extracellular zinc stimulates ERK-dependent activation of p21Cip/WAF1 and inhibits proliferation of colorectal cancer cells. Br J Pharmacol 137:597–607. doi:10.1038/sj.bjp.0704909

    Article  PubMed  CAS  Google Scholar 

  33. Archer SY, Meng S, Shei A, Hodin RA (1998) p21(WAF1) is required for butyrate-mediated growth inhibition of human colon cancer cells. Proc Natl Acad Sci USA 95:6791–6796. doi:10.1073/pnas.95.12.6791

    Article  PubMed  CAS  Google Scholar 

  34. Nicholson DW, Thornberry NA (1997) Caspases: killer protease. Trends Biochem Sci 22:299–306. doi:10.1016/S0968-0004(97)01085-2

    Article  PubMed  CAS  Google Scholar 

  35. Barnes PJ, Karin M (1997) Nuclear factor-kappa B: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336:1066–1071. doi:10.1056/NEJM199704103361506

    Article  PubMed  CAS  Google Scholar 

  36. Lind DS, Hochwald SN, Malaty J, Rekkas S, Hebig P, Mishra G, Moldawer LL, Copeland EM, MacKay S (2000) Nuclear factor-kB is upregulated in colorectal cancer. Surgery 130:363–369. doi:10.1067/msy.2001.116672

    Article  Google Scholar 

  37. Joshi SG, Francis CW, Silverman DJ, Sahni SK (2003) Nuclear factor kappa B protects against host cell apoptosis during Rickettsia rickettsii infection by inhibiting activation of apical and effector caspases and maintaining mitochondrial integrity. Infect Immun 71:4127–4136. doi:10.1128/IAI.71.7.4127-4136.2003

    Article  PubMed  CAS  Google Scholar 

  38. Taylor WR, Stark GR (2001) Regulation of the G2/M transition by p53. Oncogene 20:1803–1815. doi:10.1038/sj.onc.1204252

    Article  PubMed  CAS  Google Scholar 

  39. Itzkowitz SH, Yio X (2004) Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol 287:G7–G17. doi:10.1152/ajpgi.00079.2004

    Article  PubMed  CAS  Google Scholar 

  40. Smith AJ, Stern HS, Penner M, Hay K, Mitri A, Bapat BV, Gallinger S (1994) Somatic APC and K-ras codon 12 mutations in aberrant crypt foci from human colons. Cancer Res 54:5527–5530

    PubMed  CAS  Google Scholar 

  41. Surh YJ, Kundu JK, Na HK, Lee JS (2005) Redox-sensitive transcription factors as prime targets for chemoprevention with anti-inflammatory and antioxidative phytochemicals. J Nutr 135:2993S–3001S

    PubMed  CAS  Google Scholar 

  42. Rahman I, Marwick J, Kirkham P (2004) Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation, NF-kappaB and pro-inflammatory gene expression. Biochem Pharmacol 68:1255–1267. doi:10.1016/j.bcp.2004.05.042

    Article  PubMed  CAS  Google Scholar 

  43. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867. doi:10.1038/nature01322

    Article  PubMed  CAS  Google Scholar 

  44. Philip M, Rowley DA, Schreiber H (2004) Inflammation as a tumor promoter in cancer induction. Semin Cancer Biol 14:433–439. doi:10.1016/j.semcancer.2004.06.006

    Article  PubMed  CAS  Google Scholar 

  45. Crowell JA, Steele VE, Sigman CC, Fay JR (2003) Is inducible nitric oxide synthase a target for chemoprevention? Mol Cancer Ther 2:815–823

    PubMed  CAS  Google Scholar 

  46. Hinz B, Brune K (2002) Cyclooxygenase-2–10 years later. J Pharmacol Exp Ther 300:367–375. doi:10.1124/jpet.300.2.367

    Article  PubMed  CAS  Google Scholar 

  47. Scheller J, Ohnesorge N, Rose-John S (2006) Interleukin-6 trans-signalling in chronic inflammation and cancer. Scand J Immunol 63:321–329. doi:10.1111/j.1365-3083.2006.01750.x

    Article  PubMed  CAS  Google Scholar 

  48. Seril DN, Liao J, Yang GY, Yang CS (2003) Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animal models. Carcinogenesis 24:353–362. doi:10.1093/carcin/24.3.353

    Article  PubMed  CAS  Google Scholar 

  49. Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK, Lee SS (2001) Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res 480–481:243–268. doi:10.1016/S0027-5107(01)00183-X

    PubMed  Google Scholar 

  50. Bachschmid M, Schildknecht S, Ullrich V (2005) Redox regulation of vascular prostanoid synthesis by the nitric oxide-superoxide system. Biochem Biophys Res Commun 338:536–542. doi:10.1016/j.bbrc.2005.08.157

    Article  PubMed  CAS  Google Scholar 

  51. Nair J, Barbin A, Velic I, Bartsch H (2000) Etheno DNA-base adducts from endogenous reactive species. Mutat Res 424:59–69. doi:10.1016/S0027-5107(99)00008-1

    Google Scholar 

  52. Naziroglu M, Cay M, Ustundag B, Aksakal M, Yekeler H (1999) Protective effects of vitamin E on carbon tetrachloride-induced liver damage in rats. Cell Biochem Funct 17:253–259. doi:10.1002/(SICI)1099-0844(199912)17:4<253::AID-CBF837>3.0.CO;2-R

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This study was financially supported by Biotechnology Research Institute, Chonnam National University in 2008.

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Authors and Affiliations

  1. Molecular Biochemistry Laboratory, Biotechnology Research Institute, Chonnam National University, 300 Yongbong-Dong, Kwang-ju, 500-757, South Korea

    Sei-Jung Lee & Kye-Taek Lim

  2. Center for the Control of Animal Hazards Using Biotechnology (BK 21), Chonnam National University, 300 Yongbong-Dong, Kwang-ju, 500-757, South Korea

    Sei-Jung Lee

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Correspondence to Kye-Taek Lim.

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Lee, SJ., Lim, KT. Glycine- and proline-rich glycoprotein regulates the balance between cell proliferation and apoptosis for ACF formation in 1,2-dimethylhydrazine-treated A/J mice. Mol Cell Biochem 325, 187–197 (2009). https://doi.org/10.1007/s11010-009-0033-5

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