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St. John's Wort Attenuates Colorectal Carcinogenesis in Mice through Suppression of Inflammatory Signaling
Soumen K Manna1, Srujana Golla1, Jaya Prakash Golla1
1Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
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.
Insights
St. John's wort extract shows promise in preventing colorectal cancer. Supplementing mice diets with SJW reduced tumor development and improved survival rates by calming inflammatory pathways.
Area of Science:
- Pharmacology
- Gastroenterology
- Oncology
Background:
- Colorectal cancer (CRC) remains a significant health concern with limited preventative options.
- St. John's wort (SJW), a popular herbal remedy, has demonstrated anti-inflammatory properties but its role in CRC prevention is unexplored.
- Azoxymethane (AOM) is a widely used chemical inducer for modeling CRC in preclinical studies.
Purpose of the Study:
- To investigate the chemopreventive effects of dietary St. John's wort (SJW) extract on azoxymethane-induced colorectal carcinogenesis in a mouse model.
- To evaluate the impact of SJW supplementation on survival, tumor development, and key molecular pathways involved in CRC.
Main Methods:
- Mice were fed either a control diet or a diet supplemented with SJW extract before and during azoxymethane treatment.
- Tumor multiplicity, incidence, volume, and host physiological parameters were assessed.
- Expression and activity of Nuclear Factor kappa B (NF-κB) and Extracellular Signal-Regulated Kinase (ERK1/2) pathways were analyzed in colon tissues.
Main Results:
- SJW supplementation significantly improved survival and mitigated adverse physiological effects (weight loss, hypoalbuminemia, hypocholesterolemia) in AOM-treated mice.
- A dose-dependent reduction in tumor multiplicity, incidence of large tumors, and total tumor volume was observed in SJW-fed mice.
- SJW administration led to early and sustained attenuation of NF-κB and ERK1/2 signaling pathways in the colon epithelium.
Conclusions:
- Dietary SJW extract exhibits significant chemopreventive potential against colorectal cancer.
- SJW exerts its protective effects by attenuating pro-inflammatory signaling pathways, specifically NF-κB and ERK1/2.
- These findings support further investigation of SJW as a natural agent for colorectal cancer prevention.
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