title: Interleukin-8 enhances the effect of colchicine on cell death.
abstract: 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.
authors.affiliation: Department of Biochemical Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata 992-8510, Japan. Electronic address: 4koyama@yz.yamagata-u.ac.jp.
authors.forename: Chikako
authors.initials: C
authors.lastname: Yokoyama
authors.affiliation: Department of Materials and Life Science, Seikei University, Tokyo 180-8633, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Yajima
authors.affiliation: Department of Materials and Life Science, Seikei University, Tokyo 180-8633, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Machida
authors.affiliation: Department of Materials and Life Science, Seikei University, Tokyo 180-8633, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kawahito
authors.affiliation: Department of Materials and Life Science, Seikei University, Tokyo 180-8633, Japan.
authors.forename: Marie
authors.initials: M
authors.lastname: Uchida
authors.affiliation: Department of Materials and Life Science, Seikei University, Tokyo 180-8633, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hisatomi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D003078:Colchicine / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology*; D010179:Pancreas / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D016209:Interleukin-8; D003078:Colchicine
keywords: Colchicine; Cytokine; Interleukin-8