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Anticancer Activity of Morphine and Its Synthetic Derivative, KT-90, Mediated through Apoptosis and Inhibition of NF-κB Activation

1998; Elsevier BV; Volume: 252; Issue: 3 Linguagem: Inglês

10.1006/bbrc.1998.9695

1090-2104

Eisaburo Sueoka, Naoko Sueoka, Yasuko Kai, Sachiko Okabe, Masami Suganuma, Ken Kanematsu, Tatsuo Yamamoto, Hirota Fujiki,

Cancer Treatment and Pharmacology

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 μM) 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-α) gene expression induced by tumor promoters, okadaic acid and 12-O-tetradecanoylphorbol-13-acetate, associated with reduction of NF-κB DNA binding activity. This paper provides evidence that KT compounds confirmed the presence of anticancer activity of morphine in addition to its analgesic action.