Lucanthone

Lucanthone is orally available thioxanthone-based DNA intercalator and inhibitor of the DNA repair enzyme apurinic-apyrimidinic endonuclease 1 (APEX1 or APE1), with anti-schistosomal and potential antineoplastic activity. Lucanthone intercalates DNA and interferes with the activity of topoisomerases I and II during replication and transcription, thereby inhibiting the synthesis of macromolecules. In addition, this agent specifically inhibits the endonuclease activity of APE1, without affecting its redox activity, resulting in unrepaired DNA strand breaks which may induce apoptosis. Therefore, lucanthone may sensitize tumor cells to radiation and chemotherapy. Furthermore, lucanthone inhibits autophagy through the disruption of lysosomal function. The multifunctional nuclease APE1 is a key component for DNA repair; its expression is often correlated with tumor cell resistance to radio- and chemotherapy. Check for active clinical trials or closed clinical trials using this agent. ( NCI Thesaurus )(In Vitro):Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. To investigate the anticancer activity of Lucanthone, cell viability is measured by MTT assay. Lucanthone reduces cell viability to a similar extent in a panel of seven breast cancer cell lines. In addition, a direct comparison reveals that Lucanthone is significantly more potent than Chloroquine (CQ) at reducing breast cancer cell viability with a mean IC50 of 7.2 μM versus 66 μM for CQ. Measurement of cell viability in two representative cell lines (MDA-MB-231 and BT-20) by ATPlite assay and trypan blue exclusion reveals comparable results.