Inhibition of DNA synthesis by lonidamine and hyperthermia in human chronic myeloid leukemia cells

Lonidamine (LNA) is antitumor agent that lacks the characteristic properties of antiproliferative drugs and has narrow spectrum of antitumour effects. It is also a hyperthermia sensitizer. Hyperthermia affects on various cellular organelles, and the malignant cells are known to be more sensitive to hyperthermia. The present study examines the in vitro effects of LNA (0.01 and 0.02 mM) and hyperthermia (42 degrees C for 1 and 2 hrs) alone and in combination, on 11 human chronic myeloid leukemia cell samples. The inhibition in incorporation of 3H-thymidine was statistically significant (P less than 0.001) in human CML cells when exposed to the combination of LNA (0.01 and 0.02 mM) with hyperthermia (1 and 2 hrs) compared to the single treatment either at the same concentration of LNA at 37 degrees C or hyperthermia alone. Cytotoxicity was evaluated as the inhibition of the incorporation of 3H-thymidine in the cellular nucleic acid. The drug effects were estimated from the changes in rates of incorporation of precursor into DNA and compared with untreated control samples. Cancer cells were incubated in vitro in the presence of radioactive 3H-thymidine and drug.