Morphological Effects of Lonidamine on Two Human-Tumor Cell Culture Lines

Authors

Joseph G. Szekely, Atomic Energy of Canada Limited Research Company
Anya U. Lobreau, Atomic Energy of Canada Limited Research Company
Sabine Delaney, Atomic Energy of Canada Limited Research Company
G. Peter Raaphorst, Ontario Cancer Foundation
Mark Feeley, Ontario Cancer Foundation

Abstract

Lonidamine, 1-(2-4-dichlorobenzyl)-1-H-indazol-3-carboxylic acid. is an anticancer drug that has its primary action on cellular metabolism rather than cell division. Since lonidamine is not effective in all tumor cells, we have tested it in two human-tumor cell culture lines: MOLT-4, a T-leukemia and U-87 MG. a glioma. Lonidamine exposure of MOLT-4 cells at 50 μg/mL and pH 6.7 disrupted the mitochondria within 1 h of treatment. The mitochondria were swollen and the cristae were disrupted. When the treated cells were re-incubated in fresh medium at pH 7.4 the mitochondria rapidly returned to their normal morphology. The U-87 MG glioma cells did not show ultrastructural disruption after 1-h treatment with lonidamine at concentrations up to 200 μg/mL at pH 6.7

In the concentration range of 25 μg/mL to 200 μg/mL. lonidamine did not produce any cell killing in MOLT-4 after a 1-h exposure at pH 7.4, although the drug had some limited effectiveness at pH 6.7. Compared to sham-treated controls, long exposures to 100 μg/mL of lonidamine at pH 6.7 reduced survival in MOLT-4 to 92% and 53% after 6-h and 24-h exposures, respectively. Survival of U-87 MG glioma cells was also strongly pH dependent, a 2-h exposure to 50 μg/mL lonidamine at pH 7.4 did not cause cell death; however, survival dropped to 84% of the control at pH 6.65.

Recommended Citation

Szekely, Joseph G.; Lobreau, Anya U.; Delaney, Sabine; Raaphorst, G. Peter; and Feeley, Mark (1989) "Morphological Effects of Lonidamine on Two Human-Tumor Cell Culture Lines," Scanning Microscopy: Vol. 3: No. 2, Article 30.
Available at: https://digitalcommons.usu.edu/microscopy/vol3/iss2/30