5-aminosalicylic acid interferes in the cell cycle of colorectal cancer cells and induces cell death modes.
BACKGROUND
Epidemiological data suggests that 5-aminosalicylic acid (5-ASA), a nonsteroidal antiinflammatory drug used in the treatment of inflammatory bowel diseases, prevents colorectal cancer development in these patients, although the mechanisms remain incompletely understood.


RESULTS
Here we report that 5-ASA prevents growth of several colorectal cancer cell lines by interfering in the cell cycle, i.e., an S-phase and G2/M phase arrest, dependent on 5-ASA dosage and concentration, together with an increased mitotic index. In addition, prolonged cell cycle arrest by repeated 5-ASA treatment induced apoptosis and caused abnormal spindle organization leading to mitotic catastrophe, another form of cell death.


CONCLUSIONS
These observations illustrate that 5-ASA has chemopreventive and chemotherapeutic properties.
Department of Gastroenterology and Hepatology, and Leiden University Medical Center, Leiden, The Netherlands.
Pim J
PJ
Koelink
Marij A C
MA
Mieremet-Ooms
Willem E
WE
Corver
Kamila
K
Wolanin
Daniel W
DW
Hommes
Cornelis B H W
CB
Lamers
Hein W
HW
Verspaget
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D019804:Mesalamine / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D008941:Spindle Apparatus / Q000187:drug effects / Q000473:pathology; D000077022:Survivin
D000894:Anti-Inflammatory Agents, Non-Steroidal; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D047495:PPAR gamma; D000077022:Survivin; D019804:Mesalamine