Evaluation of IL-6 secretion by colon cancer cells treated with phytic acid
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Katedra i Zakład Biochemii, Wydział Farmaceutyczny z Oddziałem Medycyny Laboratoryjnej SUM w Katowicach
Beata Parfiniewicz   

Katedra i Zakład Biochemii, Wydział Farmaceutyczny z Oddziałem Medycyny Laboratoryjnej SUM w Katowicach 41-200 Sosnowiec, Katowicach, 41-200 Sosnowiec, ul. Narcyzow 1; tel. (32) 364 10 72
Ann. Acad. Med. Siles. 2009;63:23–31
Series of evidences have shown that interleukin-6 (IL-6) could play an important role in the pathogenesis of colon cancer. Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate, found in many plant sources and in certain high-fi ber diets. Over the past few years interest in IP6 has stemmed mostly from its potentially important antineoplastic activity against various types of cancer, including colon cancer. Moreover, it was pointed out that IP6 has ability to act on the host immune functions and infl ammatory processes by controlling the synthesis of cytokines such as IL-6. The aim of this study was to evaluate the infl uence of IP6 on IL-6 secretion by malignant epithelial colorectal Caco-2 cells.

Material and Methods:
The Caco-2 cells were treated with IP6 at the concentrations of 1.0; 2.5; 5.0 mM for 1; 6; 12 and 24 hours. The level of IL-6 was measured by enzyme-linked immunosorbent assay. The concentration of IL-6 was related to the amount of total cell protein which was estimated by the Bradford method (pg/mg).

It was found that colorectal Caco-2 cells constitutively secreted IL-6 at the constant level during 24 hour culture. IP6 down-regulated IL-6 secretion in a dose and time dependent manner. Conclusion old The present fi ndings demonstrate that IP6 in the lumen of the large intestine may play an immunoregulatory role by inducing changes in IL-6 secretion by epithelial colon cells.

Wcisło G., Szenajch J., Bodnar L. i wsp. Rak jelita grubego w świetle współczesnych badań molekularnych. Współcz. Onkol. 2006; 10: 103-110.
Kamińska J., Kowalska M., Kotowicz B., Fukasiewicz M. Cytokiny jako niezależne czynniki prognostyczne u chorych na nowotwory złośliwe. Współcz. Onkol. 2006; 10: 259-262.
Łukaszewicz M., Mroczko B., Szmitowski M. Znaczenie kliniczne interleukiny-6 (IL-6) jako czynnika rokowniczego w chorobie nowotworowej. Pol. Arch. Med. Wewn. 2007; 117: 247-251.
Ziółko E., Zych R., Bucior J. Biologiczne zależności między interleukiną-6 a szpiczakiem mnogim i ich następstwa kliniczne. Ann. Acad. Med. Siles. 2004; 58: 194-203.
Augustyniak D., Majkowska-Skrobek G., Basiewicz-Worsztynowicz B., Jankowski A. Rola kompleksu IL-6/sIL-6R oraz jego naturalnego inhibitora sgp130 w modulowaniu procesu zapalnego. Post. Biochem. 2006; 52: 194-203.
Hong D.S., Angelo L.S., Kurzrock R. Interleukin-6 and its receptor in cancer. Cancer 2007; 110: 1911-1928.
Somers W., Stahl M., Seehra J.S. A crystal structure of interleukin-6: implications for a novel mode of receptor dimerization and signaling. EMBO J. 1997; 16: 989-007.
Klimiuk P.A., Sierakowski S., Gińdzieńska-Sieśkiewicz E., Chwiećko J. Przydatność oznaczania w surowicy krwi stężeń interleukiny-6 (IL-6), metaloproteinaz i ich tkankowych inhibitorów w ocenie aktywności reumatoidalnego zapalenia stawów. Reumatologia 2005; 43: 239-242.
Becker C., Fantini M.C., Wirtz S. i wsp. IL-6 signaling promotes tumor growth in colorectal cancer. Cell Cycle 2005; 4: 217-220.
Salgado R., Junius S., Benoy I. Circulating interleukin-6 predictors survival in patients with metastatic breast cancer. Int. J. Cancer 2003; 103: 642-646.
Esfandi F., Mahammadzadeh Ghobadloo S., Basati G. Interleukin-6 level in patients with colorectal cancer. Cancer Lett. 2006; 244: 76-78.
Vucenik I., Shamshuddin A. M. Protection against cancer by dietary IP6 and inositol. Nutr. Cancer 2006; 55: 109-125.
Shamsuddin A.M. Inositol phosphates have a novel anticancer function J. Nutr. 1995; 125: 725S-732S.
Vucenik I., Shamsuddin A.M. Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic J. Nutr. 2003; 133: 3778S-3784S.
Węglarz L., Molin I., Orchel A., Parfi niewicz B Dzierżewicz Z. Quantitative analysis of the level of p53 and p21WAF1 mRNA in human colon camcer HT-29 cells treated with inositol hexaphosphate. Acta Biochim. Pol. 2006; 53: 349-356.
Węglarz L., Parfi niewicz B., Dzierżewicz Z., Wilczok T. Kwas fi ynowy jako potencjany czynnik przeciwnowotworowy jelita grubego. Gastroenterol. Pol. 2003; 10: 441-448.
Fox C.H., Eberl M. Phytic acid (IP6) novel broad spectrum anti-neoplastic agent: a systematic review. Complement. Ther. Med. 2002; 10:220-234.
Eggleton P. Eff ect of IP6 on human neutrophil cytokine production and cell morphology. Anticancer Res 1999; 19: 3711-3715.
Shirota K., LeDuy L., Yuan S.Y., Jothy S. Interleukin-6 and its receptor are expressed in human intestinal epithelial cells. Virchows Arch. Cell Pathol. Incl. Mol. Pathol. 1990; 58: 303-308.
BrozekW., Bises G., Fabjani G., Cross H. S., Peterlik M. Clone-specifi c expression, transcriptional regulation, and action of interleukin-6 in human colon carcinoma cells. BMC Cancer 2008; 8: 8-16.
Legrand-Poels S., Schoonbroodt S., Piette J. Regulation of interleukin-6 gene expression by pro-infl ammatory cytokines in a colon cancer cell line. Biochem. J. 2000; 349: 765-773.
Jung H. C., Eckmann L., Yang S. K., Panja A., Fierer J., Morzycka-Wróblewska E. A distinc array of proinfl ammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J. Clin. Invest. 1995; 95: 55-65.
Węglarz L., Wawszczyk J., Orchel A., Jaworska-Kik M., Dzierżewicz Z. Phytic acid modulates in vitro IL-8 and IL-6 release from colonic epithelial cells stimulated with LPS and IL-1 . Dig. Dis. Sci. 2007; 52: 93-102.
. Ullah A., Shamsuddin A. M., Dose-dependent inhibition of large intestinal cancer by inositol hexaphosphate in F 344 rats. Carcinogenesis 1990; 11: 2219-2222.
Verghese M., Rao D. R., Chawan L. T., Walker L. T., Shackelford L. Anticarcinogenic eff ect of phytic acid (IP6): apoptosis as a possible mechanism of action. LWT – Food Sci. Tech. 2006; 39: 1093-1098.
Węglarz L., Parfi niewicz B., Orchel A., Wawszczyk J., Kierot J. Antiproliferative and apoptocic eff ects of inositol hexaphosphate on human colon cancer Caco-2 cells. Ann. Acad. Med. Siles. 2007; 61: 477-484.
Zhang Z., Song Y., Wang X. Inositol hexaphosphate – induced enhancement of natural killer cell activity correlates with suppresion of colon carcinogenesis in rats. World J. Gastroenterol. 2005; 11: 5044-5046.