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 dru gs (NSAIDs) are potent inhibitors of colorectal carcinogenesis. However, th e major disadvantages of NSAIDs are gastrointestinal and renal toxicity. We conducted a prospective pilot study on the effects of the safe salicylic a cid 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 enem as for 14 days. Biopsies from malignant and normal tissue were taken prior to and after this treatment, Apoptosis was scored on haematoxylin/eosin-sta ined tissue sections, and cell proliferation was assessed by the proliferat ion marker Ki-67. Results: Ten out of 14 patients completed the study. The apoptotic score in creased significantly in the tumour samples (pre-treatment 14.6 +/- 1.3 vs. posttreatment 19.4 +/- 0.8; P < 0.03). The apoptotic index in the normal m ucosa 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. p ost-treatment 493 +/- 39; N.S.). There was no effect on the Ki-67 index of normal mucosa (pretreatment 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 stud ies, it may be speculated that 5-ASA could be useful in the chemoprevention of colorectal cancer.