Cell death-inducing activity of opiates in human oral tumor cell lines

Masami Kawase, Hiroshi Sakagami, Kenichiro Furuya, Hirotaka Kikuchi, Hirofumi Nishikawa, Noboru Motohashi, Yasunori Morimoto, Andreas Varga, Joseph Molnár

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

In screening cytotoxic agents in morphine alkaloids [TE1-10], codeinone [TE8] was cytotoxic against two human oral tumor cells lines (HSC-2 and HSG). The cytotoxic activity of codeinone (CC50=1.0-1.2/μg/mL) against HSC-2 or HSG cells was higher than that of doxorubicin (CC50=1.9-2.0 μg/mL). Human oral gingival fibroblasts (HGF) were relatively resistant to codeinone, as judged by higher SI ratio (3.7) suggesting the tumor-selective cytotoxicity of codeinone. The cytotoxic activity of morphine (CC50=221 μg/mL) against HSC-2 was slightly lower than that of codeine (CC50=186 μg/mL), thebaine (CC50=125 μg/mL), etorphine (CC50=94 μg/mL) or dihydroetorphine (CC50=60 μg/mL). A study of structurally-related compounds suggested that the α,β-unsaturated ketone group of codeinone was responsible for its antitumor cytotoxicity. The cytotoxic activity of codeinone was significantly reduced by N-acetylcysteine, but not affected by FeCl3, CuCl2, CoCl2, sodium ascorbate or catalase. Neither codeinone nor morphine inhibited P-glycoprotein-mediated rhodamine-123 efflux in multidrug resistant mouse T lymphoma L5178 transfected with human MDR 1 gene. These data suggest that codeinone induces cytotoxicity in oral tumor cell lines, possibly by a Michael-like addition of a protein SH or of an amino group to the bouble bond of codeinone.

Original languageEnglish
Pages (from-to)211-214
Number of pages4
JournalAnticancer research
Volume22
Issue number1 A
Publication statusPublished - May 16 2002

Keywords

  • Codeinone
  • Cytotoxic activity
  • DNA fragmentation
  • MDR reversal
  • Morphine alkaloid
  • Oral tumor cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Kawase, M., Sakagami, H., Furuya, K., Kikuchi, H., Nishikawa, H., Motohashi, N., Morimoto, Y., Varga, A., & Molnár, J. (2002). Cell death-inducing activity of opiates in human oral tumor cell lines. Anticancer research, 22(1 A), 211-214.