Anticancer activity of morphine and its synthetic derivative, KT-90, mediated through apoptosis and inhibition of NF-kappaB activation.
We recently reported that morphine inhibits growth of various human cancer cell lines (IC50/2.7-8.8 mM). We then extended the study using newly synthesized morphine derivatives, such as KT-90 and KT-87, which are analgesics 5 times more potent than morphine. KT-90 was found to inhibit growth of human cancer cell lines (IC50/42-70 microM) up to 80 times more potently than morphine. As for mechanisms of action, KT-90 and morphine induced apoptosis, and inhibited tumor necrosis factor alpha (TNF-alpha) gene expression induced by tumor promoters, okadaic acid and 12-O-tetradecanoylphorbol-13-acetate, associated with reduction of NF-kappaB DNA binding activity. This paper provides evidence that KT compounds confirmed the presence of anticancer activity of morphine in addition to its analgesic action.
Sueoka
E
E
Saitama Cancer Center Research Institute, Ina, Kitaadachi-gun, Saitama, 362-0806, Japan.
Sueoka
N
N
Kai
Y
Y
Okabe
S
S
Suganuma
M
M
Kanematsu
K
K
Yamamoto
T
T
Fujiki
H
H
D000700:Analgesics / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009020:Morphine / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010166:Palliative Care; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000700:Analgesics; D000970:Antineoplastic Agents; D009022:Morphine Derivatives; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C065295:KT 90; D009020:Morphine