Selective induction of colon cancer cell apoptosis by 5-fluorouracil in humans

To assess the mechanism of action of 5-fluorouracil (5-FU) apoptosis (AI) and proliferation (PI) indices were determined histochemically in colon carcinoma and normal colon tissue of 7 patients treated preoperatively with 5-FU (300 mg/m2/day for 5 days) and 11 controls. 5-Fluorouracil induced apoptosis selectively in malignant colonocytes (AI in 5-FU-group: 0.126 +/- 0.016 [mean +/- SEM] vs. 0.065 +/- 0.012 in controls; P < 0.05), but not in normal colonocytes. 5-Fluorouracil had no effect on the PI of either normal or malignant colonocytes. 5-Fluorouracil-induced apoptosis did not correlate with clinical outcome at 24 months. We conclude that 5-FU: (a) induces apoptosis selectively in colon cancer cells, while it spares the normal colonic mucosa, and (b) has no effect on colonocyte proliferation under the conditions of our protocol. This effect of 5-FU may contribute to its chemotherapeutic activity in human colon cancer.