Synergistic cell killing by combination therapy of retinoic acid and hyperthermia in human epidermoid laryngeal carcinoma cells in culture

In vitro monolayer culture and clonogenic assay were used to investigate th e individual and combined effect of temperature and retinoic acid (RA) on c ellular morphology and colony forming ability of human epidermoid laryngeal carcinoma (HEp-2) cells. 20 mu mol. RA alone inhibited multilayer formatio n and induced cell flattening. Hyperthermia (42 degrees C) individually cau sed formation of cytoplasmic processes and irregularities in cellular shape and size. Combined effect of hyperthermia (42 degrees C) and 20 mu mol. RA treatment caused bleb formation on cell surfaces and lysis of cytoplasmic and nuclear membrane. RA treatment also caused dose-dependent reduction of colony growth. Heat-induced cell killing was only observed at lethal temper atures of 43 degrees C and above. RA in combination with heat synergistical ly inhibited colony formation even at non lethal temperatures of 41 and 42 degrees C. These results indicate that RA in combination with hyperthermia may facilitate the therapy of human epidermoid larynx carcinoma.