Enhanced cytotoxicity of dimethylformamide by ultrasound in vitro

Polar solvents, including dimethylformamide (DMF), are investigated as anticancer drugs. The effects of a noncytotoxic DMF dose alone and with ultrasound exposure on HL-60 human promyelocytic leukemia cells grown in suspension culture are examined. The cells are insonified in a free field configuration which creates little cytotoxicity without the introduction of albumin stabilized microbubbles into the exposure chamber. When microbubbles are introduced, cytotoxicity of DMF and ultrasound is significantly higher than for ultrasound alone. The necessary presence of microbubbles for the enhanced cytotoxicity of DMF by ultrasound suggests that a likely enhancement mechanism is acoustic cavitation which should be initiated by the existence of microbubbles as nuclei. Albumin stabilized microbubbles, similar to those presently used as ultrasound contrast agents, may provide a significant source of nuclei and improve prospects for cancer therapy using acoustic cavitation.>