scholarly journals Reduction of Preneoplastic Lesions Induced by 1,2-Dimethylhydrazine in Rat Colon by Maslinic Acid, a Pentacyclic Triterpene from Olea europaea L.

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1266 ◽  
Author(s):  
M. Emília Juan ◽  
Glòria Lozano-Mena ◽  
Marta Sánchez-González ◽  
Joana M. Planas
Keyword(s):  
Colorectal Cancer ◽  
Human Cancer ◽  
Aberrant Crypt Foci ◽  
Rat Colon ◽  
Sporadic Colorectal Cancer ◽  
Sprague Dawley ◽  
Preneoplastic Lesions ◽  
Pentacyclic Triterpene ◽  
Maslinic Acid ◽  
Chemopreventive Activity

Maslinic acid triggers compelling antiproliferative and pro-apoptotic effects in different human cancer cell lines. Hence, the chemopreventive activity was investigated on early stages of carcinogenesis induced by 1,2-dimethylhydrazine (DMH) which is a model that mimics human sporadic colorectal cancer. Male Sprague-Dawley rats were orally administered either maslinic acid at 5, 10 or 25 mg/kg dissolved in (2-hydroxypropyl)-β-cyclodextrin 20% (w/v) or the solvent for 49 days. After one week of treatment, animals received three weekly intraperitoneal injections of DMH at the dose of 20 mg/kg. Maslinic acid reduced the preneoplastic biomarkers, aberrant crypt foci (ACF) and mucin-depleted foci (MDF), already at 5 mg/kg in a 15% and 27%, respectively. The decline was significant at 25 mg/kg with decreases of 33% and 51%, respectively. Correlation analysis showed a significant association between the concentrations of maslinic acid found in the colon and the reduction of ACF (r = 0.999, P = 0.019) and MDF (r = 0.997, P = 0.049). The present findings demonstrate that maslinic acid induced an inhibition of the initiation stages of carcinogenesis. The assessment of this pentacyclic triterpene at the colon sheds light for designing diets with foods rich in maslinic acid to exert a chemopreventive activity in colorectal cancer.

scholarly journals Identification of preneoplastic lesions as mucin-depleted foci in patients with sporadic colorectal cancer

2011 ◽  
Vol 103 (1) ◽  
pp. 144-149 ◽  
Author(s):  
Eiji Sakai ◽  
Takamitsu Morioka ◽  
Eiji Yamada ◽  
Hidenori Ohkubo ◽  
Takuma Higurashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Sporadic Colorectal Cancer ◽  
Preneoplastic Lesions

scholarly journals Colorectal cancer-associated microbiota contributes to oncogenic epigenetic signatures

2019 ◽  
Vol 116 (48) ◽  
pp. 24285-24295 ◽  
Author(s):  
Iradj Sobhani ◽  
Emma Bergsten ◽  
Séverine Couffin ◽  
Aurélien Amiot ◽  
Biba Nebbad ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bacterial Species ◽  
Aberrant Crypt Foci ◽  
Sporadic Colorectal Cancer ◽  
Gene Promoters ◽  
Normal Tissues ◽  
Complex Interactions ◽  
Dna Alterations ◽  
Methylation Patterns ◽  
Epigenetic Signatures

Sporadic colorectal cancer (CRC) is a result of complex interactions between the host and its environment. Environmental stressors act by causing host cell DNA alterations implicated in the onset of cancer. Here we investigate the stressor ability of CRC-associated gut dysbiosis as causal agent of host DNA alterations. The epigenetic nature of these alterations was investigated in humans and in mice. Germ-free mice receiving fecal samples from subjects with normal colonoscopy or from CRC patients were monitored for 7 or 14 wk. Aberrant crypt foci, luminal microbiota, and DNA alterations (colonic exome sequencing and methylation patterns) were monitored following human feces transfer. CRC-associated microbiota induced higher numbers of hypermethylated genes in murine colonic mucosa (vs. healthy controls’ microbiota recipients). Several gene promoters including SFRP1,2,3, PENK, NPY, ALX4, SEPT9, and WIF1 promoters were found hypermethylated in CRC but not in normal tissues or effluents from fecal donors. In a pilot study (n = 266), the blood methylation levels of 3 genes (Wif1, PENK, and NPY) were shown closely associated with CRC dysbiosis. In a validation study (n = 1,000), the cumulative methylation index (CMI) of these genes was significantly higher in CRCs than in controls. Further, CMI appeared as an independent risk factor for CRC diagnosis as shown by multivariate analysis that included fecal immunochemical blood test. Consequently, fecal bacterial species in individuals with higher CMI in blood were identified by whole metagenomic analysis. Thus, CRC-related dysbiosis induces methylation of host genes, and corresponding CMIs together with associated bacteria are potential biomarkers for CRC.

Anti-inflammatory and proapoptotic effects of umbelliferone in colon carcinogenesis

2016 ◽  
Vol 35 (10) ◽  
pp. 1041-1054 ◽  
Author(s):  
R Muthu ◽  
N Selvaraj ◽  
M Vaiyapuri
Keyword(s):  
Colorectal Cancer ◽  
Mast Cells ◽  
Inflammatory Markers ◽  
Nucleolar Organizer ◽  
Aberrant Crypt Foci ◽  
Rat Colon ◽  
Nucleolar Organizer Regions ◽  
Colon Tumorigenesis ◽  
Apoptotic Markers ◽  
Group 2

Colorectal cancer (CRC) is a serious health problem throughout the world. 5-Flurouracil, the first-line chemotherapy of colorectal cancer often produces more toxicity to neighboring cells; however, it is still used for CRC treatment. To overcome this, umbelliferone (UMB), a less toxic bioflavonoid has been used to test its anticancer effects on animal model. The objective of the present study is to evaluate the anticancer activity of UMB on 1,2-dimethylhydrazine (DMH)-induced rat colon tumorigenesis to determine the development of aberrant crypt foci (ACF), agyrophylic nucleolar organizer regions (AgNORs), mast cell recruitment, pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and also study the expressions of inducible nitric oxide synthase, cyclooxygenase (COX)-2, and apoptotic markers. DMH-induced rats showed increased ACF number (incidence), multiplicity and its distribution, counts of AgNORs, mast cells, inflammatory markers and apoptotic proteins. Interestingly, UMB supplementation to DMH-induced rats (group 4) significantly ( p < 0.05) suppressed ACF development, AgNORs, mast cells, and inflammatory markers and increased the apoptotic markers as compared to DMH-induced rats (group 2). We concluded that UMB is a potential anticancer agent that can be used for the prevention and treatment of CRC.

Aberrant crypt foci in patients with a positive family history of sporadic colorectal cancer

2007 ◽  
Vol 248 (2) ◽  
pp. 262-268 ◽  
Author(s):  
Richard G. Stevens ◽  
Helen Swede ◽  
Christopher D. Heinen ◽  
Melissa Jablonski ◽  
Michael Grupka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Positive Family History ◽  
Aberrant Crypt Foci ◽  
Sporadic Colorectal Cancer ◽  
History Of

scholarly journals Jacalin Has Chemopreventive Effects on Colon Cancer Development

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Thais Herrero Geraldino ◽  
Patricia Modiano ◽  
Luciana Chain Veronez ◽  
Milena Flória-Santos ◽  
Sergio Britto Garcia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Chemoprevention ◽  
Human Colon ◽  
Preneoplastic Lesions ◽  
Human Colon Cancer ◽  
Great Opportunity ◽  
Early Stages ◽  
Common Causes ◽  
Chemopreventive Activity

Colorectal cancer, which is one of the most common causes of cancer-related deaths worldwide, has a slow natural history that provides a great opportunity for prevention strategies. Plant-derived natural products have received considerable attention because of their inherent colorectal cancer chemopreventive effects. The plant lectin jacalin specifically recognizes the tumor-associated Thomsen-Friedenreich antigen and has antiproliferative effects on human colon cancer cells, highlighting its potential antitumor activity. To evaluate jacalin’s potential application in colorectal cancer chemoprevention, we studied its effects on the early stages of carcinogenesis. Balb/c mice were given 4 intrarectal deposits of 0.1 ml solution of Methyl-N′-Nitro-N-Nitroso-Guanidine (5 mg/ml) twice a week (with a 3-day interval) for 2 weeks. Starting 2 weeks before carcinogen administration, animals were treated orally with jacalin (0.5 and 25 μg) three times a week (on alternate weekdays) for 10 weeks. We show that jacalin treatment reduced the number of preneoplastic lesions in carcinogen-exposed mice. This anticarcinogenic activity was associated with decreased colonic epithelial cell proliferation and stromal COX-2 expression and with increased intestinal production of TNF-α. Our results demonstrate that jacalin is able to modulate the early stages of colon carcinogenesis and emphasize its promising chemopreventive activity in colorectal cancer.

scholarly journals Abnormal Savda Munziq, an Herbal Preparation of Traditional Uighur Medicine, May Prevent 1,2-dimethylhydrazine-Induced Rat Colon Carcinogenesis

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Abdiryim Yusup ◽  
Halmurat Upur ◽  
Anwar Umar ◽  
Benedicte Berke ◽  
Dilxat Yimit ◽  
...  
Keyword(s):  
Body Weight ◽  
Normal Saline ◽  
Colon Carcinogenesis ◽  
Ethanol Extract ◽  
Negative Control ◽  
Aberrant Crypt Foci ◽  
Rat Colon ◽  
Preneoplastic Lesions ◽  
Abnormal Savda ◽  
Abnormal Savda Munziq

The study tried to assess the chemoprotective effect of abnormal Savda Munziq (ASMq) on 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Male F344 rats were randomized into eight groups: Group 1 was served as control, no DMH injection was given and treated daily with normal saline. Rats in Groups 2–8 were given a single intraperitoneal injection of DMH (20 mg/kg body weight) at the beginning of the study. Group 2 was served as negative control, administered with normal saline until the end of the experiment after the single DMH injection. Groups 3–5 were served as pretreatment group, administered with ASMq ethanol extract at 400, 800 and 1600 mg/kg body weight, respectively, until the 45th day, continued by normal saline administration for another 45 days. Groups 6–8 were served as the treatment group, administered with normal saline for the first 45 days from the day of DMH injection, ASMq ethanol extract at three different doses to be administered until the end of the second 45th day. All rats were sacrificed at 91st day and the colons were analyzed for aberrant crypt foci (ACF) formation and crypt multiplicity. Results showed that ASMq ethanol extract reduced the number of ACF, AC and crypt multiplicity significantly (P< .05). It suggested that ASMq ethanol extract had chemoprotective effects on DMH-induced colon carcinogenesis, by suppressing the development of preneoplastic lesions, and probably exerted protection against the initiation and promotion steps of colon carcinogenesis.

scholarly journals Inulin Diet Intervention on Chemopreventive and Inflammatory Markers in Tumorigenesis of Colorectal Cancer

2014 ◽  
Vol 64 (4) ◽  
pp. 519-525 ◽  
Author(s):  
Hijová Emília ◽  
Szabadosova Viktoria ◽  
Štofilová Jana ◽  
Salaj Rastislav ◽  
Bomba Alojz
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Markers ◽  
Elevated Serum ◽  
Rat Colon ◽  
Control Group ◽  
Jejunal Mucosa ◽  
Sprague Dawley ◽  
Colon Tissue ◽  
Diet Intervention ◽  
Cox 2

Abstract The aim of this experiment was to investigate the infl uence of inulin administration on chemopreventive and inflammatory markers in dimethylhydrazine induced colorectal cancer development in rats. A group of 30 Sprague-Dawley rats was divided into a control group (CG), a group with dimethylhydrazine (DMH), and a group given dimethylhydrazine combined with the prebiotic (DMH+PRE). Dimethylhydrazine injection significantly (p<0.001) elevated the immunoreactivity chemopreventive markers COX-2, NFκB, iNOS, elevated serum and jejunal mucosa levels of proinfl ammatory cytokine IL-2, and decreased serum and jejunal mucosa levels of regulatory cytokine IL-10. Inulin diet intervention significantly suppressed immunoreactivity of COX- 2, NFκB, iNOS positive cells in the tunica mucosae and tela submucosae of rat colon tissue, increased levels of IL-2 and decreased levels of IL-10. By determining the chemopreventive markers COX-2, iNOS and NFkB, which can be characterized as inflammatory markers, we confirmed the presence of inflammation in the colon as the number of COX-2, NFkB and iNOS immunoreactive cells was significantly higher after DMH application than in the control group. These findings indicate that dietary intake of inulin suppressed the expression of the observed markers, which play an important role in carcinogenesis and inflammation, which predispose the use of inulin in the prevention or treatment of human chronic diseases and its use as a nutritional supplement in veterinary medicine.

Inhibition of rat colon tumors by sulindac and sulindac sulfone is independent of K-ras (codon 12) mutation

2000 ◽  
Vol 278 (2) ◽  
pp. G266-G272 ◽  
Author(s):  
Tanya A. de Jong ◽  
Stewart A. Skinner ◽  
Cathy Malcontenti-Wilson ◽  
Daphne Vogiagis ◽  
Michael Bailey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Treated Group ◽  
Rat Colon ◽  
Sprague Dawley ◽  
Ras Mutation ◽  
Ras Mutations ◽  
Mechanism Of Inhibition ◽  
Group 5

Nonsteroidal anti-inflammatory drug (NSAID) use reduces the risk of colorectal cancer by 40–50%. Previous studies suggest that effective inhibition of colorectal cancer by NSAIDs may be dependent on the presence or absence of a K-ras mutation. This study was aimed at determining the relationship between inhibition of colorectal cancer by sulindac and sulindac sulfone and the presence of activating K-ras mutations in the 1,2-dimethylhydrazine dihydrochloride rat model. Sulindac (20 mg ⋅ kg−1 ⋅ day−1), sulindac sulfone (40 mg ⋅ kg−1 ⋅ day−1), or vehicle was administered orally to male Sprague-Dawley rats for a 4-wk period beginning 20 wk after tumor induction. Tumor number and volume were measured before treatment by laparotomy and colonoscopy and again after treatment. Sulindac and sulindac sulfone treatment significantly reduced the number and volume of colorectal tumors compared with control rats. For K-ras (codon 12) mutation detection, frozen tumor tissue was collected at the endpoint. We found K-ras codon 12 mutations in 11 of 21 (52%) control tumors. The proportion of tumors with K-ras mutations in the sulindac-treated group [5 of 8 (62%); odds ratio = 1.51 (95% confidence interval = 0.29, 8.33)] and the proportion of sulindac sulfone-treated tumors [9 of 14 (64%); odds ratio = 1.63 (95% confidence interval = 0.41, 6.66)] were not significantly different from controls. Tumor inhibition did not correlate with K-ras (codon 12) mutation status, which suggests that the mechanism of inhibition of rat colorectal cancer by sulindac and sulindac sulfone is independent of K-ras mutation.

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