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Published on: May 2, 2018
An apple oligogalactan suppresses endotoxin-induced cyclooxygenase-2 expression by inhibition of LPS pathways
1Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China; Department of Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
Abstract:
Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality in developed countries. Many ingredients of apples have been proven to have anti-inflammatory and anti-carcinogenic characteristics, and show benefits for CRC prevention. The aim of this study, therefore, was to evaluate inhibitory effect of an apple oligogalactan (AOG) on pro-inflammatory endotoxin lipopolysaccharide (LPS)-activated human colon carcinoma cells HT-29 and SW-620 and investigate the possible mechanisms. The two cell lines were pretreated with AOG (0.1-1 g/L) for 30 min and then treated with 10 μg/mL LPS. Real time PCR, Western blot, electrophoretic mobility shift assay (EMSA), and ELISA were used to detect the expression and activity of cyclooxygenase-2 (COX-2), NF-κB and MAPKs pathways. AOG significantly inhibited the expression and activity of COX-2 in LPS-activated human colon carcinoma cells HT-29 and SW-620. The mechanisms of AOG-suppressed COX-2 expression may be through inhibiting the phosphorylation of MAPKs and the activation of NF-κB and AP-1. These data may provide another molecular basis for understanding how apples act to prevent CRC and indicate that AOG may be useful for treatment of colitis and prevention of carcinogenesis.
Insights
Apple oligogalactan (AOG) inhibits inflammation and cyclooxygenase-2 (COX-2) in colon cancer cells. This suggests AOG may aid in preventing colorectal cancer (CRC) and treating colitis.
Area of Science:
- Oncology
- Molecular Biology
- Nutrition Science
Background:
- Colorectal cancer (CRC) is a significant global health concern.
- Apples contain compounds with anti-inflammatory and anti-carcinogenic properties beneficial for CRC prevention.
- Apple oligogalactan (AOG) is a component of apples with potential health benefits.
Purpose of the Study:
- To investigate the inhibitory effect of AOG on lipopolysaccharide (LPS)-activated human colon carcinoma cells.
- To explore the underlying mechanisms of AOG's action on inflammatory pathways.
- To evaluate AOG's potential in CRC prevention and colitis treatment.
Main Methods:
- Human colon carcinoma cell lines (HT-29 and SW-620) were treated with AOG and LPS.
- Real-time PCR and Western blot were used to analyze gene and protein expression.
- Electrophoretic mobility shift assay (EMSA) and ELISA assessed pathway activation.
Main Results:
- AOG significantly inhibited cyclooxygenase-2 (COX-2) expression and activity in LPS-activated colon cancer cells.
- AOG suppressed the phosphorylation of MAPKs and the activation of NF-κB and AP-1 pathways.
- These mechanisms contribute to AOG's anti-inflammatory effects.
Conclusions:
- AOG demonstrates inhibitory effects on key inflammatory mediators in colon cancer cells.
- AOG's mechanisms involve the modulation of MAPK, NF-κB, and AP-1 signaling pathways.
- AOG shows promise as a therapeutic agent for colitis and a preventative measure against colorectal cancer.
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