Fructooligosaccharide and Soy Isoflavone Suppress Colonic Aberrant Crypt Foci and Cyclooxygenase-2 Expression in Dimethylhydrazine-Treated Rats

다국어 초록 (Multilingual Abstract)

This study investigated the inhibitory effects of soy isoflavones and fructooligosaccharide (FOS) on colon car-cinogenesis. Sprague-Dawley male rats were injected with 1,2-dimethylhydrazine (DMH) and given experimental diets thatcontained 0%, 3%, 6%, or 9% FOS with or without soy isoflavones (1,000 mg/kg of diet). After 12 weeks, colonic aberrantcrypt foci (ACF) formation, cyclooxygenase-2 (COX-2) expression, and fecal bile acid profiles were determined. The num-bers of ACF, the numbers of ACF containing four or more crypts per focus of colonic mucosa, and the levels of COX-2 pro-tein in the colonic epithelial tissues were significantly decreased in a dose-dependent manner in the FOS-fed, DMH-treatedrats (P. .001), as compared to the DMH-treated control rats. Soy isoflavones significantly decreased the number of ACFwith four or more aberrant crypts per focus (P. .001) and the amount of COX-2 protein (P. .01), independently of the ef-fect of the oligosaccharide. The highest suppression of ACF formation was obtained with soy isoflavones combined with . 6%FOS. No significant relationship was found between the dosage of FOS or soy isoflavones and the concentration of fecal sec-ondary bile acid. We conclude that the combination of FOS and soy isoflavones inhibits colonic ACF formation and reducesCOX-2 expression in DMH-treated rats.

참고문헌 (Reference)

1 Le Leu RK, "synbiotic combination of resistant starch and Bifidobacterium lactis facilitates apoptotic deletion of carcinogendamaged cells in rat colon" 135 : 996-1001, 2005

2 Debruyne PR, "The role of bile acids in carcinogenesis" 480-481, 2001

3 Gately S, "The contributions of cyclooxygenase-2 to tumor angiogenesis" 19 : 19-27, 2000

4 Messina M, "Soyfoods, isoflavones and risk of colonic cancer: a review of the in vitro and in vivo data" 12 : 707-728, 1998

5 Young-Sun Choi, "Soy Isoflavones Do Not Alter the Effects of Fructooligosaccharide on the Intestinal Ecosystem of Colon-Cancer Model Rats" 한국식품과학회 15 (15): 931-936, 2006

6 Pierre F, "Short-chain fructo-oligosaccharides reduce the occurrence of colon tumors and develop gut-associated lymphoid tissue in Min mice" 57 : 225-228, 1997

7 Child P, "Separation and quantitation of fatty acids, sterols and bile acids in feces by gas chromatography asthe butyl ester-acetate derivatives" 415 : 13-26, 1987

8 Booth LA, "Secondary bile acid induced DNA damage in HT29 cells: are free radicals involved?" 26 : 135-144, 1997

9 Bird RP, "Role of aberrant crypt foci in understanding the pathogenesis of colon cancer" 93 : 55-71, 1995

10 American Institute of Nutrition, "Report of the Ad Hoc Committee on Standards for Nutrition Studies" 123 : 1939-1951, 1993

11 Blume-Jensen P, "Oncogenic kinase signalling" 411 : 355-365, 2001

12 Konstantinopoulos PA, "Oestrogen receptor beta (ER ) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour’s dedifferentiation" 39 : 1251-1258, 2003

13 Bowey E, "Metabolism of isoflavones and lignans by the gut microflora; a study in germ-free and human flora-associated rats" 41 : 631-636, 2003

14 Ellington AA, "Induction of macroautophagy in human colon cancer cells by soybean B-group triterpenoid saponins" 26 : 159-167, 2005

15 Araki Y, "Hydrophilic and hydrophobic bile acids exhibit different cytotoxicities through cytolysis, interleukin-8 synthesis and apoptosis in the intestinal epithelial cell lines" 36 : 533-539, 2001

16 Salti GI, "Genistein induces apoptosis and topoisomerase II–mediated DNA breakage in colon cancer cells" 36 : 796-802, 2000

17 Hye-Young Sung, "Fructooligosaccharides Alter Profiles of Fecal Short-Chain Fatty Acidsand Bile Acids in Rats" 한국식품과학회 15 (15): 51-56, 2006

18 Eyssen HJ, "Formation of hyodeoxycholic acid from muricholic acid and hyocholic acid by an unidentified gram-positive rod termed HDCA-1 isolated from rat intestinal microflora" 65 : 3158-3163, 1999

19 Owen RW, "Faecal steroids and colorectal carcinogenesis" 222 : 76-82, 1997

20 Rao CV, "Enhancement of experimental colon cancer by genistein" 57 : 3717-3722, 1997

21 Daly KT, "Enhanced estrogenic responses and sensitivity to azoxymethane following dietary soy isoflavone supplementation in older female rats" 45 : 628-637, 2007

22 Raju J, "Energy restriction reduces the number of advanced aberrant crypt foci and attenuates the expression of colonic transforming growth factor and cyclooxygenase isoforms in Zucker obese (fa/fa) rats" 63 : 6595-6601, 2003

23 Reddy BS, "Effect of dietary oligofructose and inulin on colonic preneoplastic aberrant crypt foci inhibition" 18 : 1371-1374, 1997

24 Rowland IR, "Effect of Bifidobacterium longum and inulin on gut bacterial metabolism and carcinogen-induced aberrant crypt foci in rats" 19 : 281-285, 1998

25 Picherit C, "Dose-dependent bone-sparing effects of dietary isoflavones in the ovariectomized rat" 85 : 307-316, 2001

26 Zhang F, "Dihydroxy bile acids activate the transcription of cyclooxygenase-2" 273 : 2424-2428, 1998

27 Guo JY, "Dietary soy isoflavones and estrone protect ovariectomized ER KO and wild-type mice from carcinogen-induced colon cancer" 134 : 179-182, 2004

28 Verghese M, "Dietary inulin suppresses azoxymethane-induced preneoplastic aberrant crypt foci in mature Fisher 344 rats" 132 : 2804-2808, 2002

29 Uehara M, "Dietary fructooligosaccharides modify intestinal bioavailability of a single dose of genistein and daidzein and affect their urinary excretion and kinetics in blood of rats" 131 : 787-795, 2001

30 Lim CC, "Dietary fibres as “prebiotics”: implications for colorectal cancer" 49 : 609-619, 2005

31 WHO Technical Report Series 916, "Diet. Nutrition and the Prevention of Chronic Diseases. World Health Organization" WHO 95-104, 2003

32 조재위, "Curcumin inhibits the expression of COX-2 in UVB-irradiated human keratinocytes (HaCaT) by inhibiting activation of AP-1: p38 MAP kinase and JNK as potential upstream targets" 대한생화학ㆍ분자생물학회 37 (37): 186-192, 2005

33 Genazzani AR, "Controversial issues in climacteric medicine II. Hormone replacement therapy and cancer" 40 : 117-130, 2001

34 Gupta RA, "Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2" 1 : 11-21, 2001

35 Steele VE, "Cancer chemoprevention agent development strategies for genistein" 125(Suppl) : 713S-716S, 1995

36 Singh J, "Bifidobacterium longum, a lactic acid-producing intestinal bacterium inhibits colon cancer and modulates the intermediate biomarkers of colon carcinogenesis" 18 : 833-841, 1997

37 Kim HY, "Antiproliferative crude soy saponin extract modulates the expression of I B , protein kinase C, and cyclooxygenase-2 in human colon cancer cells" 210 : 1-6, 2004

38 Srikumar TS, "Analysis of fecal bile acids and neutral steroids using gas-liquid chromatography" 42 : 231-236, 1998

39 Kishida T, "Analysis 84 SUNG AND CHOI of bile acids in colon residual liquid or fecal material in patients with colorectal neoplasia and control subjects" 32 : 306-311, 1997

40 Pretlow TP, "Aberrant crypts correlate with tumor incidence in F344 rats treated with azoxymethane and phytate" 13 : 1509-1512, 1992

41 Takayama T, "Aberrant crypt foci of the colon as precursors of adenoma and cancer" 339 : 1277-1284, 1998

42 Ohta A, "A combination of dietary fructooligosaccharides and isoflavone conjugates increases femoral bone mineral density and equol production in ovariectomized mice" 132 : 2048-2054, 2002

43 Ioku K, "-Glucosidase activity in the rat small intestine toward quercetin monoglucosides" 62 : 1428-1431, 1998