Effect of anticancer agents on codeinone-induced apoptosis in human cancer cell lines.
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.
Takeuchi
Risa
R
Division of Anesthesiology, Department of Comprehensive Medical Sciences, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan. rtakeuch@dent.meikai.ac.jp
Hoshijima
Hiroshi
H
Onuki
Noriko
N
Nagasaka
Hiroshi
H
Chowdhury
Shahead Ali
SA
Kawase
Masami
M
Sakagami
Hiroshi
H
D000111:Acetylcysteine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D003061:Codeine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology
D000970:Antineoplastic Agents; C046414:6-codeinone; D004317:Doxorubicin; D002392:Catechin; C045651:epigallocatechin gallate; D020169:Caspases; D001205:Ascorbic Acid; D003061:Codeine; D000111:Acetylcysteine; D008727:Methotrexate