Chemoprevention of tea on colorectal cancer induced by dimethylhydrazine in Wistar rats

AIM To investigate the chemopreventiveeffects of green tea and tea pigment on 1,2-dimethylhydrazine(DMH)-induced rat colorectalcarcinogenesis.METHODS Male weaning Wistar rats wererandomly allocated into four groups.Rats in thepositive control group were given s.c.injectionof DMH,once a week for ten weeks;rats in tea-treated groups,with the same DMH treatment asin the positive group,received 2% green tea and0.1% tea pigments;rats in the negative controlgroup were given s.c.injection of the samevolume of saline as well as DMH in the positivegroup.Animals were sacrified and necropsied atthe end of week 16 and week 32.RESULTS Aberrant cryptic foci(ACF)wereformed in animals in DMH-treated groups at theend of week 16.Compared to the DMH group,green tea and tea pigments groups had less ACF(148.25 and 204.25,respectively,P【0.01).Atthe end of week 32,all rats in DMH groupdeveloped large intestinal tumors.The resultsalso showed that DMH increased labeling index(LI)of proliferating cell nuclear antigen(PCNA)of intestinal mucosa and the expression of ras-p21.However,in the tea-treated groups,PCNA-LI was significantly reduced as compared withthe positive control group(36.63 and 40.36 inthe green tea group and tea pigment group,respectively,at the end of the experiment,P【0.01).ras-p21 expression was alsosignificantly reduced(2.07 and 2.36 in the colontumors of rats in the green tea group and teapigments group,respectively at the end of theexperiment,P【0.01).Furthermore,green tea and tea pigment inhibited the expression of Bcl-2protein(2,5,1,0 and 2,4,1,0,respectively,at the end of the experiment P【0.01),andinduced expression of Bax protein(0,1,3,4and 0,1,4,3,respectively,P【0.01).CONCLUSION Chinese green tea drinkinginhibited ACF and colonic tumors formation inrats,which showed that tea had a significantchemopreventive effect on DMH-inducedcolorectal carcinogenesis.Such effects may bedue to suppression of cell proliferation andinduction of apoptosis in the intestinal crypts.

Epigallocatechin gallate inhibits dimethylhydrazine-induced colorectal cancer in rats

BACKGROUND Epigallocatechin gallate(EGCG)is a polyhydroxy phenolic compound extracted from tea and its antitumor effect has received widespread attention.We explored the inhibitory effect of EGCG on dimethylhydrazine(DMH)-induced colorectal cancer(CRC)using a rat model,predicted the interaction between EGCG and CRC target genes using a database,and explained the EGCG associated target pathways and mechanisms in CRC.AIM To understand the inhibitory mechanisms of EGCG on CRC cell proliferation and identify its pharmacological targets by network pharmacology analysis.METHODS DMH(40 mg/kg,s.c.,twice weekly for eight weeks)was used to induce CRC in rats.After model establishment,the rats were administered with EGCG(50,100,or 200 mg/kg,p.o.,once daily for eight weeks)and killed 12 and 20 wk after the start of the experiment.Formation of aberrant crypt foci and tumor was studied by histological analysis.Using network pharmacology analysis,candidate and collective targets of EGCG and CRC were identified,and Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes analyses were used to predict the pathways altered by EGCG.RESULTS At week 12,high-dose EGCG treatment significantly reduced the tumor formation rate,total number of tumors,cancerous and non-cancerous tumors,tumor volume,ascites formation,and aberrant crypt foci count.At week 20,all three doses of EGCG were effective.Seventy-eight collective targets of EGCG and CRC were identified,of which 28 genes were dysregulated in CRC.Kyoto Encyclopedia of Genes and Genomes and GO analyses showed that the dysregulated genes were enriched in hsa05210(CRC),hsa04115(p53 signaling pathway),and hsa04151(PI3K-Akt signaling pathway),GO:0043124(negative regulation of I-kappaB kinase/NF-kappaB signaling pathway),GO:0043409(negative regulation of mitogen-activated protein kinase cascade),and GO:2001244(positive regulation of intrinsic apoptotic signaling pathway)respectively.CONCLUSION EGCG inhibits the formation of DMH-induced CRC by regulating key pathways involved in tumorigenesis.

Selenium as a chemopreventive agent in experimentally induced colon carcinogenesis

AIM:To elucidate the chemopreventive efficacy of selenium during experimentally induced colon carcinogenesis.METHODS:Thirty-two male wistar rats were divided into four groups:group □(normal control);group □[1,2-dimethylhydrazine(DMH) treated];group □ (selenium treated);and group □ (DMH + selenium treated).Groups □ and □ were given subcutaneous injections of DMH(30 mg/kg body weight) every week for 20 wk.Selenium,in the form of sodium selenite,was given to groups □ and at 1 ppm in drinking water ad libitum for 20 wk.At the end of the study,rats were sacrificed and their colons were analyzed for the development of tumors,antioxidant enzyme levels and histological changes.RESULTS:100 of the DMH treated rats developed tumors,which was reduced to 60 upon simultaneous selenium supplementation.Similarly,tumor multiplicity decreased to 1.1 following selenium supplementation to DMH treated rats.Levels of lipid peroxidation,glutathione-S-transferase,superoxide dismutase(SOD),catalase,and glutathione peroxidase(GPx) decreased following DMH treatment,whereas levels of glutathione(GSH) and glutathione reductase(GR) significantly increased in DMH treated rats.Selenium administration to DMH treated rats led to an increase in the levels of lipid peroxidation,SOD,catalase,glutathione-S-transferase and GPx,but decreased the levels of GSH and GR.Histopathological studies on DMH treated rats revealed dysplasia of the colonic histoarchitecture,which showed signs of improvement following selenium treatment.CONCLUSION:The study suggests the antioxidative potential of selenium is a major factor in providing protection from development of experimentally induced colon carcinogenesis.

Ethanolic Extract of <i>Nigella sativa</i>Seeds Lacks the Chemopreventive Efficacy in the Post Initiation Phase of DMH-Induced Colon Cancer in a Rat Model

Nigella sativa, belonging to the Ranunculacea family, is a versatile phytochemical mine bestowed with multi-dimensional medicinal effects. The current study was performed to investigate the chemopreventive efficacy, if any, of the ethanolic extract of indigenous Nigella sativa seeds (ENS) and to evaluate its potentials on tumor progression during the initiation and post initiation phases of Dimethylhydrazine-induced colon carcinogenesis in a rat model. ENS treatment during the initiation phase unveiled chemopreventive effect manifested by significant reductions in tumor incidence, multiplicity and tumor volumes. Histopathological findings and modified Duke’s classification of tumors provided evidence that ENS, administered in the initiation phase, is capable of delaying progression, restricting invasion and attenuating aggressiveness of colon tumors. These results imply that ENS may be a promising candidate in the primary prevention of colon cancer. On the contrary, we demonstrated that ENS lacked chemopreventive and tumorigenesis inhibitory effects in the post initiation phase. We speculate that the chemopreventive effect of ENS might be due to the synergistic actions of various constituents present in the extract. However, extensive studies are warranted and more efforts need to be dedicated to fractionate, analyze and to further appraise the anticancer effect of ENS before any definitive conclusions can be drawn.