Cytotoxicity of beta-lapachone, an o-naphthoquinone with possible therapeutic use

beta -lapachone (beta -lap) is a lipophilic o-naphthoquinone isolated from the bark of the lapacho tree. Initial observations proved its capability fo r inhibiting growth of Yoshida tumor and Walker 256 carcinosarcoma. beta -L ap redox-cycling in the presence of reductants and oxygen yields "reactive oxygen species" (ROS: O-2(-), OH and H2O2) which cytotoxicity led to assume its role in D-lap activity in cells. beta -Lap inhibited DNA synthesis in Trypanosoma cruzi as well as topoisomerases I and II, poly(ADP-ribose) poly merase (PARP) in different cells. These enzymes are essential for maintaini ng DNA structure. beta -Lap inhibited growth of a large variety of tumor ce lls including epidermoid laringeal cancer, prostate, colon, ovary and breas t cancer and also different types of leukemia cells. Advances in knowledge of apoptosis ("programmed cell death") and necrosis provided useful informa tion for understanding the mechanism of beta -lap cytotoxicity. Thiol-depen dent proteases (Calpaine), kinases (e.g. c-JUN NH2-terminal kinase), caspas es and nucleases are involved in beta -lap cytotoxicity. These enzymes acti vity, as well as ROS production by B-lap redoxcycling, would be essential f or beta -lap cytotoxicity. Diaphorase and NAD(P)H-quinone reductase, which catalyse beta -lap redox-cycling and ROS production, seem to play an essent ial role in beta -lap activity. On these grounds, clinical applications of beta -lap have been suggested.