TRAIL induces apoptosis in human colorectal adenoma cell lines and human colorectal adenomas.
OBJECTIVE
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.


METHODS
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.
Jalving
Mathilde
M
Department of Gastroenterology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
de Jong
Steven
S
Koornstra
Jan J
JJ
Boersma-van Ek
Wytske
W
Zwart
Nynke
N
Wesseling
Jelle
J
de Vries
Elisabeth G E
EG
Kleibeuker
Jan H
JH
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D008024:Ligands; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology*
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D008024:Ligands; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D020169:Caspases