title: Colon cancer chemopreventive effects of baicalein, an active enteric microbiome metabolite from baicalin.
abstract: Baicalin is a major constituent of Scutellaria baicalensis, which is a commonly used herbal medicine in many Asian countries. After oral ingestion, intestinal microbiota metabolism may change parent compound's structure and its biological activities. However, whether baicalin can be metabolized by enteric microbiota and the related anticancer activity is not clear. In this study, using human enteric microbiome incubation and HPLC analysis, we observed that baicalin can be quickly converted to baicalein. We compared the antiproliferative effects of baicalin and baicalein using a panel of human cancer cell lines, including three human colorectal cancer (CRC) cell lines. In vitro antiproliferative effects on CRC cells were verified using an in vivo xenograft nude mouse model. Baicalin showed limited antiproliferative effects on some of these cancer cell lines. Baicalein, however, showed significant antiproliferative effects in all the tested cancer cell lines, especially on HCT-116 human colorectal cancer cells. In vivo antitumor results supported our in vitro data. We demonstrated that baicalein exerts potent S phase cell cycle arrest and pro-apoptotic effects in HCT-116 cells. Baicalein induced the activation of caspase 3 and 9. The in silico modeling suggested that baicalein forms hydrogen bonds with residues Ser251 and Asp253 at the active site of caspase 3, while interactions with residues Leu227 and Asp228 in caspase 9 through its hydroxyl groups. Data from this study suggested that baicalein is a potent anticancer metabolite derived from S. baicalensis. Enteric microbiota play a key role in the colon cancer chemoprevention of S. baicalensis.
authors.affiliation: Τang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.affiliation: Τang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Zhang
authors.affiliation: Τang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Lina
authors.initials: L
authors.lastname: Chen
authors.affiliation: Τang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Anderson
authors.affiliation: Τang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Lu
authors.affiliation: Τang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D044950:Flavanones / Q000008:administration & dosage* / Q000378:metabolism; D005419:Flavonoids / Q000378:metabolism; D000069196:Gastrointestinal Microbiome; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry* / Q000378:metabolism; D031364:Scutellaria baicalensis
chemical_list: D044950:Flavanones; D005419:Flavonoids; D010936:Plant Extracts; C499814:Scutellaria baicalensis extract; C038044:baicalin; C006680:baicalein