Anticancer activity of morphine and its synthetic derivative, KT-90, mediated through apoptosis and inhibition of NF-kappaB activation.

Abstract

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.

• Authors: E Sueoka, N Sueoka, Y Kai, S Okabe, M Suganuma, K Kanematsu, T Yamamoto, H Fujiki
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 252 Issue 3 Pg. 566-70 (Nov 27 1998) ISSN: 0006-291X [Print] United States
• PMID: 9837747 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 1998 Academic Press.

Chemical References

• Analgesics
• Antineoplastic Agents
• Morphine Derivatives
• NF-kappa B
• Tumor Necrosis Factor-alpha
• KT 90
• Morphine

Topics

• Analgesics (pharmacology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Division (drug effects)
• Electrophoresis, Polyacrylamide Gel
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Morphine (pharmacology)
• Morphine Derivatives (pharmacology)
• NF-kappa B (antagonists & inhibitors)
• Palliative Care
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (metabolism)