In vitro activity: TAS-103 dihydrochloride (also known as BMS-247615) is a dual inhibitor of DNA topoisomerase I/II. It is a quinoline derivative that displays antitumor activity in murine and human tumor models. TAS-103 is active on CCRF-CEM cells with an IC50 value of 5 nM. TAS-103 at 0.1 μM significantly increases levels of topo IIα FITC immunofluorescence in individual CCRF-CEM cells. TAS-103 inhibits the viability of HeLa cells, with an IC50 of 40 nM. TAS-103 at 10 μM disrupts signal recognition particle (SRP) complex formation, and induces destabilization of SRP14 and SRP19 and its eventual degradation. Although TAS-103 has been reported to be a potent topoisomerase II poison. However, other studies have indicated that cellular susceptibility to TAS-103 is not correlated with topoisomerase II expression. TAS-103 (30 mg/kg, i.v.) causes significant tumor growth suppression in mice bearing Lewis lung carcinoma (LLC) cells, without obvious body weight loss, and the liposomal TAS-103 is more active than free TAS-103.

Cell Assay: CCRF-CEM human acute lymphoblastic leukaemia cells are grown in RPMI-1640 supplemented with 3 mM l-glutamine, 10% foetal bovine serum, 50 U/mL of penicillin, and 40 μg/mL of streptomycin at 37°C in a humidified atmosphere containing 5% CO2. TAS-103, CPT and DACA are dissolved in DMSO. Exponentially growing cells (~5 × 105) are exposed to either of the drugs for 2 hrs. Following drug exposure, cells are washed twice by centrifugation (400 × g, 3 min) in cold phosphate-buffered saline