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Published on: May 14, 2016
Low molecular weight apple polysaccharides induced cell cycle arrest in colorectal tumor
1Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Shaanxi, P.R. China.
Abstract:
Dietary components play an important role in cancer prevention. Many ingredients from apples have been proven to have antitumor potency. We thus made low molecular weight apple polysaccharides (LMWAP) and evaluated the effects of it on colorectal cancer (CRC). The effects of LMWAP on human colon carcinoma cells (HT-29) were evaluated using a microarray. Then, cell-cycle distribution was measured by flow cytometric analysis. A colitis-associated colorectal cancer mouse model was used to assess the effect of LMWAP on in vivo CRC prevention. Treatment of HT-29 cells with LMWAP resulted in 333 genes expression over cutoff values (≥2-fold). Further analysis demonstrated that pathways of cell cycle were mainly influenced. At the concentrations from 0.001 to 0.1 mg/mL, LMWAP induced a G(0)/G(1) phase block in HT-29 cells in a dose-dependent way. In vivo studies revealed that administration of LMWAP could protect ICR mice against CRC effectively. The results of Western blot suggested LMWAP induced cell-cycle arrest in a p53 independent manner. These data indicate that LMWAP could inhibit the development of CRC through affecting cell cycle, and it has potential for clinical prevention for colon cancer.
Insights
Low molecular weight apple polysaccharides (LMWAP) show potential for colorectal cancer (CRC) prevention. LMWAP effectively inhibits CRC development by inducing cell-cycle arrest in a p53-independent manner.
Area of Science:
- Oncology
- Nutritional Science
- Biochemistry
Background:
- Dietary components are crucial for cancer prevention.
- Apple-derived compounds exhibit antitumor properties.
Purpose of the Study:
- To investigate the anti-colorectal cancer (CRC) effects of low molecular weight apple polysaccharides (LMWAP).
- To evaluate LMWAP's impact on human colon carcinoma cells (HT-29) and in a mouse model.
Main Methods:
- Microarray analysis of HT-29 cells treated with LMWAP.
- Flow cytometry for cell-cycle distribution analysis.
- Colitis-associated CRC mouse model for in vivo efficacy assessment.
- Western blot to determine p53 pathway involvement.
Main Results:
- LMWAP treatment altered gene expression in HT-29 cells, significantly impacting cell cycle pathways.
- LMWAP induced a dose-dependent G(0)/G(1) phase cell cycle arrest in HT-29 cells.
- In vivo studies demonstrated LMWAP's protective effect against CRC in mice, independent of the p53 pathway.
Conclusions:
- LMWAP inhibits colorectal cancer development by modulating cell cycle progression.
- LMWAP exhibits potential as a preventative agent for colon cancer.
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