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

Abstract
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 alpha,beta-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.
AuthorsRisa Takeuchi, Hiroshi Hoshijima, Noriko Onuki, Hiroshi Nagasaka, Shahead Ali Chowdhury, Masami Kawase, Hiroshi Sakagami
JournalAnticancer research (Anticancer Res) 2005 Nov-Dec Vol. 25 Issue 6B Pg. 4037-41 ISSN: 0250-7005 [Print] Greece
PMID16309196 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • 6-codeinone
  • Doxorubicin
  • Catechin
  • epigallocatechin gallate
  • Caspases
  • Ascorbic Acid
  • Codeine
  • Acetylcysteine
  • Methotrexate
Topics
  • Acetylcysteine (pharmacology)
  • Antineoplastic Agents (pharmacology)
  • Apoptosis (drug effects)
  • Ascorbic Acid (pharmacology)
  • Carcinoma, Squamous Cell (drug therapy, pathology)
  • Caspases (metabolism)
  • Catechin (analogs & derivatives, pharmacology)
  • Cell Line, Tumor
  • Codeine (analogs & derivatives, pharmacology)
  • Dose-Response Relationship, Drug
  • Doxorubicin (pharmacology)
  • Drug Synergism
  • HL-60 Cells
  • Humans
  • Methotrexate (pharmacology)

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