Mesalazine-induced apoptosis of colorectal cancer: on the verge of a new chemopreventive era?
BACKGROUND
It is an accepted fact that non-steroidal anti-inflammatory drugs (NSAIDs) are potent inhibitors of colorectal carcinogenesis. However, the major disadvantages of NSAIDs are gastrointestinal and renal toxicity. We conducted a prospective pilot study on the effects of the safe salicylic acid derivative, mesalazine, on apoptosis and proliferation of tumour cells and on normal tissue in colorectal cancer patients.


METHODS
Patients with colorectal cancer were asked to take mesalazine enemas for 14 days. Biopsies from malignant and normal tissue were taken prior to and after this treatment. Apoptosis was scored on haematoxylin/eosin-stained tissue sections, and cell proliferation was assessed by the proliferation marker Ki-67.


RESULTS
Ten out of 14 patients completed the study. The apoptotic score increased significantly in the tumour samples (pre-treatment 14.6 +/- 1.3 vs. post-treatment 19.4 +/- 0.8; P < 0.03). The apoptotic index in the normal mucosa was unchanged (pre-treatment 3.1 +/- 0.4 vs. post-treatment 2.9 +/- 0.3; N.S.). The cell proliferation in malignant tissue, according to the Ki-67 score, was hardly affected by mesalazine (pre-treatment 522 +/- 38 vs. post-treatment 493 +/- 39; N.S.). There was no effect on the Ki-67 index of normal mucosa (pre-treatment 24.2 +/- 2.0 vs. post-treatment 28.3 +/- 2.0; N.S.).


CONCLUSIONS
This pilot study conducted in patients with colorectal cancer clearly shows that mesalazine selectively induces apoptosis of tumour cells. On the basis of these findings, which need to be confirmed in larger studies, it may be speculated that 5-ASA could be useful in the chemoprevention of colorectal cancer.
Bus
P J
PJ
Department of Gastroenterology-Hepatology, Leiden University Medical Centre, Leiden, The Netherlands.
Nagtegaal
I D
ID
Verspaget
H W
HW
Lamers
C B
CB
Geldof
H
H
Van Krieken
J H
JH
Griffioen
G
G
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000517:prevention & control*; D004733:Enema; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D019394:Ki-67 Antigen; D019804:Mesalamine