In a phase I investigation of the safety and tolerability of beta-lapachone, healthy volunteers received either single doses of 300 mg or 400 mg; or multiple doses of 100 mg or 200 mg.

Human non-small cell lung cancer cell lines H1299 and NCI-H358 were grown in RPMI-1640 containing 10% heat-inactivated fetal bovine serum and 100U/mL each of penicillin and streptomycin. Cultures were incubated at 37 deg-C in a 5% CO2 atmosphere. Cells were seeded in 96-well plates and incubated for 24 hours then treated with 0, 1, 2, or 3 micro-M of beta-lapachone for another 24 and 48 hours. The percentage of viable cells was determined by using a CellTiter96 Aqueous One Cell Proliferation Assay Kit. Beta-lapachone decreased the viability of both H1299 and NCI-H358 in a dose- and time-dependent manner. The maximal decrease was observed at 48 h relative to the levels at 24 h. DAPI staining was carried out under a confocal microscope to investigate the morphological changes related to apoptosis. Beta-lapachone treated cells exhibited nuclear fragmentation at a concentration of 1, 2 and 3 micro-M after 48 hours.