Beta-Lapachone

ARQ-501 is a naphthoquinone compound derived from bark of Tabebuia sp., with antitumor, antibacterial, antifungal and antitrypanosomal activities. Beta-lapachone exerts its anti-tumor effect by indirect actions of inducing p53-independent apoptosis and cell cycle arrest mediated through altered activities of cell cycle control regulatory proteins; including down-regulating retinoblastoma protein (pRB), a transcriptional repressor target at transcription factor E2F-1, as well as induces expression of cyclin dependent kinase inhibitor 1A (CDKN1A or p21) . Both E2F-1 and p21 are required for G1/S-phase transition during cell cycle. This agent also inhibits DNA topoisomerase I by a mechanism distinct from that of camptothecin, and thereby blocks the formation of a cleavable complex leading to enzyme inhibition and prevent DNA repair. Furthermore, beta-lapachone could induce reactive oxygen species in vivo, and result in cytotoxicity. (In Vitro) :β-Lapachone is a topoisomerase I inhibitor. β-Lapachone (25 μM) inhibits camptothecin-induced DNA cleavage.β-Lapachone (10-40 μM) significantly reduces the colony-forming ability of CHO cells, and is cytotoxic in S phase. β-Lapachone at above 10 μM, causes a heavy DNA-strand breaks in CHO cells.β-Lapachone (10 μM) suppresses JCPyV replication in IMR-32 cells. β-Lapachone (1.0 μM) potently affects JCPyV propagation in JCI cells. β-Lapachone (0.01-0.1 μM) inhibits VP1 production in JCI cells. (In Vivo) :β-Lapachone (0.066%) ameliorates cisplatin-induced renal injury and when in combination with cisplatin, the affect is more significant in mice. β-Lapachone increases Mre11-Rad50-Nbs1 (MRN) complex expression in mice.