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.
Copyright 1998 Academic Press.