ErgosterolperoxidefromChagamushroom (Inonotus obliquus) exhibits anti-cancer activitybydown-regulationofthe β-catenin pathwayin colorectalcancer

Title
ErgosterolperoxidefromChagamushroom (Inonotus obliquus) exhibits anti-cancer activitybydown-regulationofthe β-catenin pathwayin colorectalcancer
Authors
Ju-Hee KangJeong-Eun JangSiddhartha Kumar Mishra이희주노주원Dongyun ShinMirim JinMi Kyung KimChangsun CholSeung Hyun Oh
Keywords
Ergosterolperoxide; Colorectal cancer; AOM/DSS; β-catenin; Chaga mushroom
Issue Date
2015-09
Publisher
Journal of ethnopharmacology
Citation
VOL 173, 303-312
Abstract
Aim ofthestudy: In thisstudy,weexaminedtheeffectofdifferentfractionsandcomponentsofChaga mushroom (Inonotus Obliquus) on viabilityandapoptosisofcoloncancercells.Amongthem,onecom- ponent showedthemosteffectivegrowthinhibitionandwasidentified asergosterolperoxidebyNMR analysis.Weinvestigatedtheanti-proliferativeandapoptosismechanismsofergosterolperoxideasso- ciated withitsanti-canceractivitiesinhumancolorectalcancer(CRC)celllinesandtesteditsanti-tumor effect oncolitis-inducedCRCdevelopedbyAzoxymethane(AOM)/Dextransulfatesodium(DSS)ina mouse model. Materials andmethods: WeusedMTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) assays, flow cytometryassays,Westernblotanalysis,colonyformationassays,reversetranscription- polymerasechainreaction(RT-PCR),immunohistochemistry(IHC),andAOM/DSSmousemodelstostudy the molecularmechanismofmetastaticactivitiesinCRCcells. Results: Ergosterolperoxideinhibitedcellproliferationandalsosuppressedclonogeniccolonyformation in HCT116,HT-29,SW620andDLD-1CRCcelllines.ThegrowthinhibitionobservedintheseCRCcell lines wastheresultofapoptosis,whichwasconfirmed byFACSanalysisandWesternblotting.Ergosterol peroxideinhibitedthenuclearlevelsof β-catenin, whichultimatelyresultedinreducedtranscriptionof c-Myc,cyclinD1,andCDK-8.Ergosterolperoxideadministrationshowedatendencytosuppresstumor growthinthecolonofAOM/DSS-treatedmice,andquantification oftheIHCstainingshowedadramatic decrease intheKi67-positivestainingandanincreaseintheTUNELstainingofcolonicepithelialcellsin AOM/DSS-treatedmicebyergosterolperoxideforbothpreventionandtherapy. Conclusion: Our datasuggestthatergosterolperoxidesuppressestheproliferationofCRCcelllinesand effectivelyinhibitscolitis-associatedcoloncancerinAOM/DSS-treatedmice.Ergosterolperoxidedown- regulated β-catenin signaling,whichexertedanti-proliferativeandpro-apoptoticactivitiesinCRCcells. These propertiesofergosterolperoxideadvocateitsuseasasupplementincoloncancerc
URI
http://pubs.kist.re.kr/handle/201004/50119
ISSN
03788741
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KIST Publication > Article
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