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International Journal of Colorectal Disease

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Open Access 01-11-2012 | Original Article

The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells

Authors: Małgorzata Kapral, Joanna Wawszczyk, Magdalena Jurzak, Andrzej Hollek, Ludmiła Węglarz

Published in: International Journal of Colorectal Disease | Issue 11/2012

Abstract

Introduction

Matrix metalloproteinases (MMPs) have repeatedly been shown to play a very active role in extracellular matrix degradation associated with tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for their ability to inhibit MMP activity thereby inhibiting malignant progression. Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell adhesion and migration. In the present study, the effect of IP6 on the expression of MMP and TIMP genes was evaluated in unstimulated and IL-1β-stimulated colon cancer cell line Caco-2.

Materials and methods

Real-time QRT-PCR was used to validate the transcription level of selected MMP and TIMP genes in Caco-2 cells after treatment with 1 ng/ml of IL-1β, 2.5 mM of IP6, and both for 6, 12, and 24 h.

Results

Stimulation of cells with IL-1β only resulted in an overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1β in 6 h lasting culture. After 12 h, IL-1β-induced MMP-2 mRNA expression was significantly reduced by IP6.

Conclusion

Proinflammatory cytokine IL-1β upregulates MMP and TIMP mRNAs expression in colon cancer epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both MMP and TIMP genes and downregulates IL-1β stimulated transcription of some of these genes. IP6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion.

Mantovani A, Garlanda C, Allavena P (2010) Molecular pathways and targets in cancer-related inflammation. Ann Med 42:161–170PubMedCrossRef

Perwez Hussain S, Harris CC (2007) Inflammation and cancer: an ancient link with novel potentials. Int J Cancer 12:2373–2380CrossRef

Apte RN, Voronov E (2008) Is interleukin-1 a good or bad ‘guy’ in tumor immunobiology and immunotherapy? Immunol Rev 222:222–241PubMedCrossRef

Lewis AM, Varghese S, Hui Xu H, Alexander HR (2006) Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment. J Transl Med 4:48PubMedCrossRef

Deryugina EI, Quigley JP (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25:9–34PubMedCrossRef

Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nature Rev 2:161–174CrossRef

Kajita M, Itoh Y, Chiba T, Mori H, Okada A, Kinoh H, Seiki M (2001) Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. J Cell Biol 153:893–904PubMedCrossRef

Nagase H, Visse R, Murphy G (2006) Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 69:562–573PubMedCrossRef

Roeb E, Arndt M, Jansen B, Schumpelick V, Matern S (2004) Simultaneous determination of matrix metalloproteinase (MMP)-7, MMP-1, -3, and -13 gene expression by multiplex PCR in colorectal carcinomas. Int J Colorectal Dis 19:518–524PubMedCrossRef

10.

Yamada T, Oshima T, Yoshihara K, Tamura S, Kanazawa A, Inagaki D, Yamamoto N, Sato T, Fujii S, Numata K, Kunisaki C, Shiozawa M, Morinaga S, Akaike M, Rino Y, Tanaka K, Masuda M, Imada T (2010) Overexpression of MMP-13 gene in colorectal cancer with liver metastasis. Anticancer Res 30:2693–2699PubMed

11.

Zhang M, Zhu GY, Gao HY, Zhao SP, Xue Y (2011) Expression of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric adenocarcinoma. J Surg Oncol 103:243–247PubMedCrossRef

12.

von Lampe B, Barthel B, Coupland SE, Riecken E-O, Rosewicz S (2000) Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease. Gut 47:63–73CrossRef

13.

Heuschkel RB, MacDonald TT, Moneleone G, Baja-Elliott M, Walker Smith JA, Pender SLF (2000) Imbalance of stromelysin-1 and TIMP-1 in the mucosal lesion of children with inflammatory bowel disease. Gut 47:57–62PubMedCrossRef

14.

Hidalgo M, Eckhardt SG (2001) Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst 93:178–193PubMedCrossRef

15.

Baker AH, Edwards DR, Murphy G (2002) Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J Cell Sci 115:3719–3727PubMedCrossRef

16.

Jiang Z, Goldberg ID, Shi Z (2002) Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene 21:2245–2252PubMedCrossRef

17.

Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM (2000) Matrix metalloproteinases biological activity and clinical implications. J Clin Oncol 18:1135–1149PubMed

18.

Duncan AM (2004) The role of nutrition in the prevention of breast cancer. AACN Clin Issues 15:119–135PubMedCrossRef

19.

Orzechowski A, Ostaszewski P, Jank M, Berwid SJ (2002) Bioactive substances of plant origin in food—impact on genomics. Reprod Nutr Dev 42:461–477PubMedCrossRef

20.

Ferguson LR, Harris PJ (1999) Protection against cancer by wheat bran: role of dietary fibre and phytochemicals. Eur J Cancer Prev 8:17–25PubMedCrossRef

21.

Szwergold BS, Graham RA, Brown TR (1987) Observation of inositol pentakis- and hexakis-phosphates in mammalian tissues by 31P NMR. Biochem Biophys Res Commun 149:874–881PubMedCrossRef

22.

Matejuk A, Shamsuddin A (2010) IP6 in cancer therapy: past, present and future. Curr Cancer Ther Rev 6:1–12CrossRef

23.

Jenab M, Thompson LU (1998) The influence of phytic acid in wheat bran on early biomarkers of colon carcinogenesis. Carcinogenesis 19:1087–1092PubMedCrossRef

24.

Norazalina WM, Hairuszah I, Norashareena MS (2010) Anticarcinogenic efficacy of phytic acid extracted from rice bran on azoxymethane-induced colon carcinogenesis in rats. Exp Toxicol Pathol 62:259–268PubMedCrossRef

25.

Shamsuddin AM, Vucenik I (2005) IP6 and inositol in cancer prevention and therapy. Curr Cancer Ther Rev 1:259–269CrossRef

26.

Vucenik I, Shamsuddin AM (2006) Protection against cancer by dietary IP6 and inositol. Nutr Cancer 55:109–125PubMedCrossRef

27.

Ferry S, Matsuda M, Yoshida H, Hirata M (2002) Inositol hexakisphosphate blocks tumor cell growth by activating apoptotic machinery as well as by inhibiting the Akt/NFκB-mediated cell survival pathway. Carcinogenesis 23:2031–2041PubMedCrossRef

28.

Bozsik A, Kökény S, Olah E (2007) Molecular mechanisms for the antitumor activity of inositol hexakisphosphate (IP6). Cancer Genomics Proteomics 4:43–51PubMed

29.

Raina K, Rajamanickam S, Singh RP, Agarwal R (2008) Chemopreventive efficacy of inositol hexaphosphate against prostate tumor growth and progression in TRAMP mice. Clin Cancer Res 14:3177–31784PubMedCrossRef

30.

Tantivejkul K, Vucenik I, Shamsuddin AM (2003) Inositol hexaphosphate (IP6) inhibits key events of cancer metastasis: I. In vitro studies of adhesion migration and invasion of MDA-MB 231 human breast cancer cells. Anticancer Res 23:3671–3679PubMed

31.

Kapral M, Wawszczyk J, Jurzak M, Dymitruk D, Węglarz L (2010) Evaluation of the expression of metalloproteinases 2 and 9 and their tissue inhibitors in colon cancer cells treated with phytic acid. Acta Pol Pharm 67:625–629PubMed

32.

Rath T, Roderfeld M, Graf J, Wagner S, Vehr AK, Dietrich C, Geier A, Roeb E (2006) Enhanced expression of MMP-7 and MMP-13 in inflammatory bowel disease: a precancerous potential? Inflamm Bowel Dis 12:1025–1035PubMedCrossRef

33.

Coussens LM, Fingleton B, Matrisian LM (2002) Matrix metalloproteinase inhibitors and cancer: trials and ribulations. Science 295:2387–2392PubMedCrossRef

34.

Fingleton B (2006) Matrix metalloproteinases: roles in cancer and metastasis. Front Biosci 11:479–491PubMedCrossRef

35.

Vihinen P, Kähäri VM (2002) Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer 99:157–166PubMedCrossRef

36.

Raddatz D, Bockemuhl M, Ramadori G (2005) Quantitative measurement of cytokine mRNA in inflammatory bowel disease: relation to clinical and endoscopic activity and outcome. Eur J Gastroenterol Hepatol 17:547–557PubMedCrossRef

37.

Hussain S, Assender JW, Bond M, Wong LF, Murphy D, Newby AC (2002) Activation of protein kinase C zeta is essential for cytokine-induced metalloproteinase-1, -3, and -9 secretion from rabbit smooth muscle cells and inhibits proliferation. J Biol Chem 277:27345–27352PubMedCrossRef

38.

Xie Z, Singh M, Singh K (2004) Differential regulation of matrix metalloproteinase-2 and -9 expression and activity in adult rat cardiac fibroblasts in response to interleukin-1beta. J Biol Chem 279:39513–39519PubMedCrossRef

39.

Gan X, Wong B, Wright SD, Cai T-Q (2001) Production of matrix metalloproteinase-9 in CaCO-2 cells in response to inflammatory stimuli. J Interferon Cytokine Res 21:93–98PubMedCrossRef

40.

Brinckerhoff CE, Rutter JL, Benbow U (2000) Interstitial collagenases as markers of tumor progression. Clin Cancer Res 6:4823–4830PubMed

41.

Bendardaf R, Buhmeida A, Ristamäki R, Syrjänen K, Pyrhönen S (2007) MMP-1 (collagenase-1) expression in primary colorectal cancer and its metastases. Scand J Gastroenterol 42:1473–1478PubMedCrossRef

42.

Westermarck J, Kähäri VM (1999) Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 13:781–792PubMed

43.

Kermorgant S, Aparicio T, Dessirier V, Lewin MJ, Lehy T (2001) Hepatocyte growth factor induces colonic cancer cell invasiveness via enhanced motility and protease overproduction. Evidence for PI3 kinase and PKC involvement. Carcinogenesis 22:1035–1042PubMedCrossRef

44.

Claramunt RM, Bouissane L, Cabildo MP, Cornago MP, Elguero J, Radziwon A, Medina C (2009) Synthesis and biological evaluation of curcuminoid pyrazoles as new therapeutic agents in inflammatory bowel disease: effect on matrix metalloproteinases. Bioorg Med Chem 17:1290–1296PubMedCrossRef

45.

Salmela MT, Pender SLF, Karjalainen-Lindsberg M-L, Puolakkainen P, MacDonald TT, Saarialho-Kere U (2004) Collagenase-1 (MMP-1), matrilysin-1 (MMP-7), and stromelysin-2 (MMP-10) are expressed by migrating enterocytes during intestinal wound healing. Scand J Gastroenterol 39:1095–1104PubMedCrossRef

46.

Kasaoka T, Nishiyama H, Okada M, Nakajima M (2008) Matrix metalloproteinase inhibitor, MMI270 (CGS27023A) inhibited hematogenic metastasis of B16 melanoma cells in both experimental and spontaneous metastasis models. Clin Exp Metastasis 25:827–834PubMedCrossRef

47.

Roy R, Yang J, Moses MA (2009) Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol 27:5287–5297PubMedCrossRef

48.

Castro MM, Tanus-Santos JE, Gerlach RF (2011) Matrix metalloproteinases: targets for doxycycline to prevent the vascular alterations of hypertension. Pharmacol Res 64:567–572PubMedCrossRef

49.

Dejonckheere E, Vandenbroucke RE, Libert C (2011) Matrix metalloproteinases as drug target in ischemia/reperfusion injury. Drug Discov Today 16:762–778PubMed

50.

Castro MM, Kandasamy AD, Youssef N, Schulz R (2011) Matrix metalloproteinase inhibitor properties of tetracyclines: therapeutic potential in cardiovascular diseases. Pharmacol Res 64:551–560PubMedCrossRef

51.

Cox TR, Erler JT (2011) Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer. Dis Model Mech 4:165–178PubMedCrossRef

52.

Zucker S, Vacirca J (2004) Role of matrix metalloproteinases (MMPs) in colorectal cancer. Cancer Metastasis Rev 23:101–117PubMedCrossRef

53.

Hu J, Van den Steen PE, Houde M, Ilenchuk TT, Opdenakker G (2004) Inhibitors of gelatinase B/matrix metalloproteinase-9 activity comparison of a peptidomimetic and polyhistidine with single-chain derivatives of a neutralizing monoclonal antibody. Biochem Pharmacol 67:1001–1009PubMedCrossRef

54.

Krzystyniak KL (2002) Current strategies for anticancer chemoprevention and chemoprotection. Acta Pol Pharm 59:473–478PubMed

55.

Huang C, Ma WY, Hecht SS, Dong Z (1997) Inositol hexaphosphate inhibits cell transformation and activator protein 1 activation by targeting phosphatidylinositol-3′ kinase. Cancer Res 57:2873–2878PubMed

56.

Kapral M, Parfiniewicz B, Strzałka-Mrozik B, Zachacz A, Weglarz L (2008) Evaluation of the expression of transcriptional factor NF-kappaB induced by phytic acid in colon cancer cells. Acta Pol Pharm 65:697–702PubMed

Title: The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells
Authors: Małgorzata Kapral
Joanna Wawszczyk
Magdalena Jurzak
Andrzej Hollek
Ludmiła Węglarz
Publication date: 01-11-2012
Publisher: Springer-Verlag
Published in: International Journal of Colorectal Disease / Issue 11/2012
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-012-1445-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells

Abstract

Introduction

Materials and methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Materials and methods

Results

Conclusion

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