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: Soumen K Manna, Srujana Golla, Jaya Prakash Golla, Naoki Tanaka, Yan Cai, Shogo Takahashi, Kristopher W Krausz, Tsutomu Matsubara, Ilia Korboukh, Frank J Gonzalez
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 8 Issue 9 Pg. 786-95 (Sep 2015) ISSN: 1940-6215 [Electronic] United States
• PMID: 26069204 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Anticarcinogenic Agents
• NF-kappa B
• Oligonucleotides
• Plant Extracts
• Extracellular Signal-Regulated MAP Kinases
• Azoxymethane

Topics

• Animals
• Anticarcinogenic Agents (therapeutic use)
• Azoxymethane (chemistry)
• Carcinogenesis (drug effects)
• Cell Transformation, Neoplastic (drug effects)
• Colon (pathology)
• Colorectal Neoplasms (drug therapy, prevention & control)
• Diet
• Dietary Supplements
• Disease Models, Animal
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Hypericum (chemistry)
• Inflammation (drug therapy)
• Male
• Mice
• NF-kappa B (metabolism)
• Oligonucleotide Array Sequence Analysis
• Oligonucleotides (chemistry)
• Plant Extracts (therapeutic use)
• Signal Transduction (drug effects)