Plant sterols in their free forms are known to inhibit colon cancer. Whether these activities persist when compounds are incorporated into processed food is not reported yet. This study aimed to test the ability of plant sterol esters (PSE) incorporated into a nonpuffed extruded food (NPE) model to inhibit colon carcinogenesis. PSE was added into NPE at four concentrations (0.0%, 0.7%, 1.4%, and 2.1%). PSE-NPE activity was tested in azoxymethane/dextran sodium sulfate-induced Balb/c mice. The groups given PSE-NPE did not show any colon tumor formation. Immunohistochemistry results revealed that the group fed with 1.4% PSE had the lowest histoscore for cyclooxygenase-2 expression and the highest histoscore for cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9expressions. The results of this study indicated that even after incorporation into a food system, which is processed using high pressure and temperature, PSE retained its chemopreventive activity. The proposed mechanisms are by suppressing inflammation and inducing apoptosis.
Get full access to this article
View all access options for this article.
References
1.
FitzmauriceC, DickerD, PainA, et al.: The global burden of cancer 2013. JAMA Oncol, 2015; 1:505–527.
2.
GLOBOCAN 2012: Estimated Cancer Incidence, Mortality, and Prevalence Worldwide in 2012. www.globocan.iarc.fr (accessed February2017).
3.
BirtDF, PhillipsGJ: Diet, genes, and microbes: Complexities of colon cancer prevention. Toxicol Pathol, 2014; 42:182–188.
4.
JainT, BathlaS: Plant sterols form human health Bergman—A review. J Appl Nat Sci, 2015; 7:1081–1087.
5.
VanmierloT, HuscheC, SchöttHF, PetterssonH, LütjohannD: Plant sterol oxidation products—Analogs to cholesterol oxidation products from plant origin?. Biochimie, 2013; 95:464–472.
6.
PlatJ, MensinkRP: Plant stanol and sterol esters in the control of blood cholesterol levels: Mechanism and safety aspects. Am J Cardiol, 2005; 96:15–22.
7.
MendilaharsuM, StefaniED, Deneo-PellegriniH, CarzoglioJ, RoncoA: Phytosterols and risk of lung cancer: A case-control study in Uruguay. Lung Cancer, 1998; 21:37–45.
8.
De StefaniE, BoffettaP, RoncoAL, et al.: Plant sterols and risk of stomach cancer: A case-control study in Uruguay. Nutr Cancer, 2000; 37:140–144.
9.
McCannSE, FreudenheimJL, MarshallJR, GrahamS: Risk of human ovarian cancer is related to dietary intake of selected nutrients, phytochemicals and food groups. J Nutr, 2003; 133:1937–1942.
10.
AwadAB, RoyR, FinkCS: Beta-sitosterol, a plant sterol, induces apoptosis and activates key caspases in MDA-MB-231 human breast cancer cells. Oncol Rep, 2003; 2:497–500.
11.
ReyesMMDL, OyongGG, EbajoVD, et al.: Cytotoxic triterpenes and sterols from Pipturus arborescens (Link) C.B. Rob. J App Pharm Sci, 2015; 5:23–30.
12.
MericJ, RotteyS, OlaussenK, et al.: Cyclooxygenase-2 as a target for anticancer drug development. Crit Rev Oncol Hematol, 2006; 59:51–64.
13.
BaskarA, IgnacimuthuS, PaulrajGM, NumairKS: Chemopreventive potential of β-sitosterol in experimental colon cancer model—An in vitro and in vivo study. BMC Complement Altern Med, 2010; 10:24–34.
14.
RoussiS, WinterA, GosseF, et al.: Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells. Cell Death Differ, 2005; 12:128–135.
15.
LanYH, ChiangJH, HuangWW, et al.: Activations of both extrinsic and intrinsic pathways in HCT-116 human colorectal cancer cells contribute to apoptosis through p53-mediated atm/fas signaling by Emilia sonchifolia extract, a folklore medicinal plant. Evid Based Complement Alternat Med, 2012; 2012:178178.
16.
ChoiYH, KongKR, KimYA, KilJH, ParkKY: Induction of Bax and activation of caspases during beta-sitosterol-mediated apoptosis in human colon cancer cells. Int J Oncol, 2003; 23:1657–1662.
17.
ZhaS, YegnasubramanianV, NelsonWG, IsaacsWB, De MarzoAM: Cyclooxygenases in cancer: Progress and perspective. Cancer Lett, 2004; 215:1–20.
18.
MeirerK, SteinhilberD, ProschakE: Inhibitors of the arachidonic acid cascade: Interfering with multiple pathways. Basic Clin Pharmacol Toxicol, 2014; 114:83–91.
19.
CatalanoE: Role of Phytochemicals in the Chemoprevention of Tumors. www.arxiv.org (accesed June2016).
20.
DuboisRN, AbramsonSB, CroffordL, et al.: Cyclooxygenase in biology and disease. FASEB J, 1998; 12:1063–1073.
21.
SuzukiR, KohnoH, SugieS, NakagamaH, TanakaT: Strain differences in the susceptibility to azoxymethane and dextran sodium sulfate-induced colon carcinogenesis in mice. Carcinogenesis, 2006; 27:162–169.
22.
JanezicSA, RaoAV: Dose-dependent effects of dietary phytosterol on epithelial cell proliferation of the murine colon. Food Chem Toxicol, 1992; 30:611–616.
23.
SinghV, MoreauRA, HickKB: Yield and phytosterol composition of oil extracted from grain sorghum and its wet-milled fractions. Cereal Chem, 2003; 80:126–129.
24.
YamayaA, EndoY, FujimotoK, KitamuraK: Effects of genetic variability and planting location on the phytosterol content and composition in soy bean seeds. Food Chem, 2007; 102:1071–1075.
25.
OzdestanO, ErolT, AcarB: Phytosterols in rice bran and usage of rice bran in food industry. In: 9th Baltic Conference on Food Science and Technology “Food for Consumer Well-Being,”2014; pp. 24–27.
26.
LoganathanR, SelvadurayKR, NaseretnamK, RadhakrishnanAK: Health promoting effects of phytonutrients found in palm oil. Malays J Nutr, 2010; 16:309–322.
27.
ReevesPG, NielsenFR, FaheyGC: AIN-93 purified diets for laboratory rodents: Final report of the American institute of nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr, 1993; 123:1939–1951.
KanterM, CoskunO, KorkmazA, OterS: Effects of Nigela sativa on oxidative stress and β-cell damaged in streptozotocin-induced diabetic rats. Anat Rec, 2004; 279A:685–691.
30.
HuinaR, SongbaiL: Comparison of normal and reverse phase column in phytosterol detection by high performance liquid chromatography (HPLC). J Zhejiang Univ (Agric Life Sci), 2013; 39:233–236.
31.
LeguizamonC, WellerCL, SchegelVL, CarrTP: Plant sterol and policosanol characterization of hexane extracts from grain sorghum, corn, and their DDGS. J Am Oil Chem Soc, 2009; 86:707–716.
32.
AspNG, JohanssonCG, HallmerH, SiljestromM: Rapid enzymatic assay of insoluble and soluble dietary fiber. J Agric Food Chem, 1983; 31:476–482.
33.
XuZ, GodberJS: Comparison of supercritical fluid and solvent extraction methods in extracting γ-oryzanol from rice bran. J Am Oil Chem Soc, 2000; 77:547–551.
34.
HorwitzW, LatimerGW: Alpha-tocopherol and alpha-tocopheryl acetate in foods and feeds. Colorimetric method. In: Official Method of Analysis of AOAC International 2005, 18th Ed.: Gaithersburg MD, Method 971.30, pp. 30–34.
35.
SahreenS, KhanMR, KhanRA: Evaluation of antioxidant activities of various solvent extracts of Carissa opaca fruits. Food Chem, 2010; 122:1205–1211.
36.
ChangC, YangM, WenH, ChernJ: Estimation of total flavonoid content in propolis by two complementary colorimetric methods. J Food Drug Anal, 2002; 10:178–182.
37.
PalozzaP, SeriniS, MaggianoN, et al.: β-carotene downregulates the steady-state and heregulin-α-induced COX-2 pathways in colon cancer cells. J Nutr, 2005; 135:129–136.
GhoshN, ChakiR, MandalV, MandalSC: COX-2 as a target for cancer chemotherapy. Pharmacol Rep, 2010; 62:233–244.
40.
NunesT, BernardazziC, de SouzaHS: Cell death and inflammatory bowel diseases: Apoptosis, necrosis, and autophagy in the intestinal epithelium. Biomed Res Int, 2014; 2014:218493.
41.
KalimuthuS, KimSK: Cell survival and apoptosis signaling as therapeutic target for cancer: Marine bioactive compounds. Int J Mol Sci, 2013; 14:2334–2354.
42.
GhobrialIM, WitzigTE, AdjeiAA: Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin, 2005; 55:178–194.
43.
FanY, BergmanA: The cleave-Caspase-3 antibody is a marker of Caspase-9-like DRONC activity in Drosophila. Cell Death Differ, 2010; 17:534–539.
44.
KimYS, LiXF, KangKH, RyuB, KimSK: Stigmasterol isolated from marine microalgae Navicula incerta induces apoptosis in human hepatoma HepG2 cells. BMB Rep, 2014; 47:433–438.
45.
WongRSY: Apoptosis in cancer: From pathogenesis to treatment. J Exp Clin Cancer Res, 2011; 30:87–101.
DjefafliaB, VasseurS, GuillaumondF: Lipid metabolic reprogramming in cancer cells. Oncogenesis, 2016; 5:e189.
48.
Hac-WydroK, WydroP, JagodaA, KapustaJ: The study on the interaction between phytosterols and phospholipids in model membranes. Chem Phys Lipids, 2007; 150:22–34.
49.
DoganS, HuX, ZangY, et al.: Effects of high-fat diet and/or body weight on mammary tumor leptin and apoptosis signaling pathways in MMTV-TGF-α mice. Breast Cancer Res, 2007; 9:91–105.
50.
CantrillR: Phytosterols, phytostanols and their esters. www.fao.org (accessed November2015).
51.
WakaiK, DateC, FukuiM, et al.: Dietary fiber and risk of colorectal cancer in the japan collaborative cohort study. Cancer Epidemiol Biomarkers Prev, 2007; 16:668–675.
StoneWL, KrishnanK, CampbellSE, et al.: Tocopherols and the treatment of colon cancer. Ann NY Acad Sci, 2004; 1031:223–233.
55.
WachA, PyrzyńskaK, BiesagaM: Quercetin content in some food and herbal samples. Food Chem, 2007; 100:699–704.
56.
YangK, LamprechtSA, LiuY, et al.: Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon. Carcinogenesis, 2000; 21:1655–1660.
57.
AcklandML, Van de WaarsenburgS, JonesR: Synergistic antiproliferative action of the flavonols quercetin and kaempferol in cultured human cancer cell lines. In Vivo, 2005; 19:69–76.
58.
GiftsonJS, JayanthiS, NaliniN: Chemopreventive efficacy of gallic acid, an antioxidant and anticarcinogenic polyphenol, against 1,2-dimethyl hydrazine induced rat colon carcinogenesis. Invest New Drugs, 2010; 28:251–259.
59.
SubramanianAP, JaganathanSK, MandalM, SupriyantoE, MuhamadII: Gallic acid induced apoptotic events in HCT-15 colon cancer cells. World J Gastroenterol, 2016; 22:3952–3961.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
