Enhancement of the cytotoxicity of mistletoe lectin-1 (ML-1) by high pH or perturbation in Golgi functions

Journal/Book: Pharmazie 46 (5), 349-351. 1991;

Abstract: We have studied the cytotoxicity of Mistletoe lectin-1 (ML-1), acytotoxic protein produced by Viscum album, in CHO and V79 cells and inmutant cell lines altered in Golgi functions or in endosomalacidification. In wild-type CHO cells, cytotoxicity of ML-1 was greatlyenhanced by ammonium chloride or nigericin. A CHO mutant defective inendosomal acidification (DMPR-2), which is resistant to diphtheriatoxin, modeccin and Pseudomonas aeruginosa exotoxin A and hypersensitiveto ricin, showed increased sensitivity to ML-1. MonR-31 and MF-1 aremonensin- and compactin-resistant mutants derived from CHO and V79 celllines, respectively, and are presumably altered in Golgi functions. Thecytotoxicity of ML-1 was found to be increased in both MonR-31 and MF-1cells as compared with their parental cells. These results indicate thatthe effects of chemicals or mutations altering endosomal acidificationand Golgi functions on the cytotoxicity of ML-1 are similar to those onricin cytotoxicity. Our results suggest that the cytotoxicity of ML-1 isenhanced by an increase in endosomal pH, as well as by chemicals ormutations altering the structure/functions of the Golgi regions. Likericin, the intoxication process of ML-1 may involve the Golgi regions.Author.

Keyword(s): AMMONIUM-CHLORIDE/PD (pharmacology)

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