Selective Induction of Colon Cancer Cell Apoptosis by 5-Fluorouracil in Humans

Abstract

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.

Overexpression of Krüppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity

“…In RKO-EcR-KLF4 cells treated with Ponasterone A to induce KLF4, we see no evidence of nuclear condensation, chromatin fragmentation, apoptotic bodies, or plasma membrane disruption. In contrast, RKO-EcR-KLF4 cells treated with 5-FU, a known proapoptotic agent (Rigas et al, 2002), exhibit these morphological changes. Figure 4b shows results of electrophoresis of genomic DNA from RKO-EcR and RKO-EcR-KLF4 cells treated with Ponasterone A, ethanol, or 5-FU.…”

Apoptosis and chemo‐resistance in colorectal cancer

“…Apoptosis is one such important cellular response and both in vitro and in vivo studies have effectively demonstrated that activation of the apoptotic pathways contributes to the cytotoxic action of most chemotherapeutic drugs [45,46]. Both 5-FU and oxaliplatin, two of the main chemotherapeutic agents used in treatment of advanced CRC act by selective induction of apoptosis in colon cancer cells [47,48]. Also combination treatment with 5-FU and irinotecan has been shown to induce apoptosis in various colon carcinoma cell lines [49,50].…”

Inhibition of NF-Kappa B augments sensitivity to 5-Fluorouracil/Folinic acid in colon cancer1

“…Like most chemotherapeutic agents, 5-FU alone and in conjunction with folinic acid induces marked apoptosis in sensitive cells. Specifically, 5-FU has been shown to induce apoptosis in colonocytes and colon cancer cells [4,5].…”