Effect of anticancer agents on codeinone-induced apoptosis in human cancer cell lines

Risa Takeuchi, Hiroshi Hoshijima, Noriko Onuki, Hiroshi Nagasaka, Shahead Ali Chowdhury, Masami Kawase, Hiroshi Sakagami

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14 Citations (Scopus)


The possible apoptosis-inducing activity of codeinone, an oxidative metabolite of codeine, without or with anticancer drugs, was investigated. Codeinone induced internucleosomal DNA fragmentation in human promyelocytic leukemia cells (HL-60), but not in human squamous cell carcinoma cells (HSC-2). Codeinone dose-dependently activated caspase-3 in both of these cells, but to a much lesser extent than that attained by actinomycin D. This property of codeinone was similar to what we have found previously in α,β- unsaturated ketones. Codeinone did not activate caspase-8 or caspase-9 in these cells. The cytotoxic activity of codeinone against HSC-2 cells was inhibited by N-acetyl-L-cysteine, but somewhat additively stimulated by sodium ascorbate, epigallocatechin gallate, hydrogen peroxide, sodium fluoride, 5-fluorouridine, cisplatin, doxorubicin and methotrexate. These data suggest that codeinone has possible antitumor potential, in addition to its action as a narcotic analgesic, even though it induces incomplete apoptosis-associated characteristics.

Original languageEnglish
Pages (from-to)4037-4041
Number of pages5
JournalAnticancer Research
Issue number6 B
Publication statusPublished - 2005 Nov


  • Anticancer drugs
  • Apoptosis
  • Caspase-3
  • Codeinone
  • DNA fragmentation
  • α,β-unsaturated ketones


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