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

Biochem Biophys Res Commun. 1998 Nov 27;252(3):566-70. doi: 10.1006/bbrc.1998.9695.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

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