title: St. John's Wort Attenuates Colorectal Carcinogenesis in Mice through Suppression of Inflammatory Signaling.
abstract: Despite widespread use as well as epidemiologic indications, there have been no investigations into the effect of St. John's wort (SJW) extract on colorectal carcinogenesis in vivo. This study reports a systematic evaluation of the impact of dietary supplementation of SJW extract on azoxymethane-induced colorectal carcinogenesis in mice. Mice were fed with either AIN-93G (control) diet or SJW extract-supplemented diet (SJW diet) prior to azoxymethane treatment. SJW diet was found to significantly improve the overall survival of azoxymethane-treated mice. Pretreatment with the SJW diet significantly reduced body weight loss as well as decrease of serum albumin and cholesterol levels associated with azoxymethane-induced colorectal tumorigenesis. SJW diet-fed mice showed a significant decrease in tumor multiplicity along with a decrease in incidence of large tumors and a trend toward decreased total tumor volume in a dose-dependent manner. A short-term study, which examined the effect of SJW prior to rectal bleeding, also showed decrease in colorectal polyps in SJW diet-fed mice. Nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinase (ERK1/2) pathways were attenuated by SJW administration. SJW extract resulted in early and continuous attenuation of these pathways in the colon epithelium of SJW diet-fed mice under both short-term and long-term treatment regimens. In conclusion, this study demonstrated the chemopreventive potential of SJW extract against colorectal cancer through attenuation of proinflammatory processes.
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Soumen K
authors.initials: SK
authors.lastname: Manna
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Srujana
authors.initials: S
authors.lastname: Golla
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Jaya Prakash
authors.initials: JP
authors.lastname: Golla
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Shogo
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Kristopher W
authors.initials: KW
authors.lastname: Krausz
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Matsubara
authors.affiliation: Syncon, Inc., Atwood, California.
authors.forename: Ilia
authors.initials: I
authors.lastname: Korboukh
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. gonzalef@mail.nih.gov.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001397:Azoxymethane / Q000737:chemistry; D063646:Carcinogenesis / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D004032:Diet; D019587:Dietary Supplements; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020902:Hypericum / Q000737:chemistry*; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000737:chemistry; D010936:Plant Extracts / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016588:Anticarcinogenic Agents; D016328:NF-kappa B; D009841:Oligonucleotides; D010936:Plant Extracts; D048049:Extracellular Signal-Regulated MAP Kinases; D001397:Azoxymethane