Interleukin-8 enhances the effect of colchicine on cell death.

Pro-inflammatory cytokines are known to be generated in tumors and play important roles in angiogenesis, mitosis, and tumor progression. However, few studies have investigated the synergistic effects of pro-inflammatory cytokines and anticancer drugs on cell death. In the present study, we examined the combined effects of pro-inflammatory cytokines and colchicine on cell death of cancer cells. Colchicine induces G2/M arrest in the cell cycle by binding to tubulin, one of the main constituents of microtubules. SUIT-2 human pancreatic cancer cell line cells overexpressing pro-inflammatory cytokines, including interleukin (IL)-1β, IL-8, and tumor necrosis factor (TNF)-α, were treated with colchicine. The effect of colchicine on cell death was enhanced in cells overexpressing IL-8. Moreover, the effect of colchicine on cell death was enhanced in cells overexpressing two IL-8 up-regulators, NF-κB and IL-6, but not in cells overexpressing an IL-8 down-regulator, splicing factor proline/glutamine-rich (SFPQ). Synergistic effects of IL-8 and colchicine were also observed in cells overexpressing IL-8 isoforms lacking the signal peptide. Therefore, IL-8 appeared to function as an enhancer of cell death in cancer cells treated with colchicine. The present results suggest a new role for IL-8 related to cell death of cancer cells.