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.
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Authors | Risa Takeuchi, Hiroshi Hoshijima, Noriko Onuki, Hiroshi Nagasaka, Shahead Ali Chowdhury, Masami Kawase, Hiroshi Sakagami |
Journal | Anticancer research
(Anticancer Res)
2005 Nov-Dec
Vol. 25
Issue 6B
Pg. 4037-41
ISSN: 0250-7005 [Print] Greece |
PMID | 16309196
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- 6-codeinone
- Doxorubicin
- Catechin
- epigallocatechin gallate
- Caspases
- Ascorbic Acid
- Codeine
- Acetylcysteine
- Methotrexate
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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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