Basic–alimentary tract5-ASA Affects Cell Cycle Progression in Colorectal Cells by Reversibly Activating a Replication Checkpoint
Section snippets
Cell Lines
HT29 (mutant p53R273H), LoVo (hMSH2 mutant), and HCT116 (hMLH1 mutant) colorectal cancer cells were obtained from the ATCC. HCT116p53−/− cells (p53 null) were originated in Prof. Burt Vogelstein’s laboratory as described.24 HCT116+chr3 (hMLH1 wild-type) were a kind gift from Dr. Boland’s laboratory.25 Cells were grown in monolayers in Iscove’s modified Dulbecco’s medium (IMDM; GIBCO/Invitrogen, Lofer, Austria) containing 2 nmol/L glutamine and 10% fetal bovine serum (FBS) at 5% CO2. The medium
5-ASA Reduces the Proliferation of Human Colon Cancer Cell Lines
The effect of 5-ASA on cellular viability and cellular growth was evaluated by an assay based on the activity of mitochondrial dehydrogenase, which cleaves a soluble yellow tetrazolium salt (MTT) to blue formazan crystals, a conversion that occurs only in living cells. HCT116, LoVo, and HT29 cells were treated with 5-ASA (0–20 mmol/L) for 48 hours. 5-ASA treatment induced a significant concentration-dependent reduction in the proliferation of all cell lines (Figure 1).
5-ASA Affects Cell Cycle Progression in CRC Cells
We aimed to establish
Discussion
The convincing clinical evidence for chemopreventive effect of 5-ASA in patients with IBD has prompted studies of its molecular mechanisms of action. It is generally believed that 5-ASA has specific activities other than anti-inflammatory or oxygen scavenging that interferes with carcinogenesis.
Our group has previously shown that 5-ASA decreases the rate of spontaneous mutations in colon cancer cells, which was independent from the presence of a functional mismatch repair complex,23 thus
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Supported by the Austrian Science Fund (grants M-874-B14 to M.G.L. and P18270 to C.G.); by the International Organization of Inflammatory Bowel Diseases; and by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.