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Updated: Aug 7, 2026
In vitro Organoid Culture of Primary Mouse Colon Tumors
Published on: May 17, 2013
TRAIL induces apoptosis in human colorectal adenoma cell lines and human colorectal adenomas
Mathilde Jalving1, Steven de Jong, Jan J Koornstra
1Department of Gastroenterology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Purpose:
Recombinant human (rh) tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential new anticancer drug which can induce apoptosis in colorectal cancer cell lines. The aim of this study was to investigate whether it is possible to induce apoptosis in human adenoma cell lines and human adenomas using rhTRAIL.
Experimental Design:
Two human adenoma cell lines were exposed to 0.1 microg/mL of rhTRAIL for 5 hours. Apoptosis and caspase activation in cell lines were evaluated using immunocytochemistry, fluorimetric caspase assays, and Western blotting. Short-term explant cultures were established from freshly removed human adenomas (n = 38) and biopsies of normal colon epithelium (n = 15), and these were incubated for 5 hours in the presence or absence of 1 microg/mL of rhTRAIL. Apoptosis was determined in paraffin-embedded tissue using morphologic criteria and cleaved caspase-3 staining.
Results:
In the adenoma cell lines, rhTRAIL induced up to 55% apoptosis. This coincided with caspase-8 and caspase-3 activation and could be inhibited by a pan-caspase inhibitor. rhTRAIL induced caspase-dependent apoptosis in adenomas with high-grade dysplasia (n = 21) compared with the paired untreated counterparts (apoptotic index, 34 +/- 5% versus 17 +/- 2%, mean +/- SE; P = 0.002), but not in adenomas with low-grade dysplasia (n = 17) or in normal colon epithelium (n = 15).
Conclusions:
Colorectal adenoma cell lines and adenomas with high-grade dysplasia are sensitive to rhTRAIL-induced apoptosis, whereas normal colon epithelium is not. This suggests the potential application of rhTRAIL in the treatment of adenomas with high-grade dysplasia.
Insights
Recombinant human TRAIL induces apoptosis in colorectal adenoma cell lines and high-grade dysplasia adenomas. Normal colon cells and low-grade adenomas were not affected, suggesting TRAIL
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) shows potential as an anticancer therapeutic.
- TRAIL is known to induce apoptosis in colorectal cancer cell lines.
Purpose of the Study:
- To investigate the efficacy of rhTRAIL in inducing apoptosis in human adenoma cell lines and primary human adenomas.
- To determine if rhTRAIL can selectively target pre-cancerous colorectal lesions.
Main Methods:
- Adenoma cell lines and human adenoma/normal colon explants were treated with rhTRAIL.
- Apoptosis was assessed using immunocytochemistry, caspase assays, Western blotting, and morphologic criteria.
- Cleaved caspase-3 staining was used to quantify apoptosis in tissue samples.
Main Results:
- rhTRAIL induced up to 55% apoptosis in adenoma cell lines, accompanied by caspase-8 and caspase-3 activation.
- Apoptosis was significantly induced in high-grade dysplasia adenomas (34% +/- 5%) but not in low-grade dysplasia adenomas or normal colon epithelium.
- The observed apoptosis was caspase-dependent and could be inhibited by a pan-caspase inhibitor.
Conclusions:
- Colorectal adenoma cell lines and high-grade dysplasia adenomas are sensitive to rhTRAIL-induced apoptosis.
- Normal colon epithelium and low-grade dysplasia adenomas do not exhibit sensitivity to rhTRAIL.
- rhTRAIL demonstrates potential as a therapeutic agent for treating high-grade dysplasia in colorectal adenomas.
