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Comparative cyto toxic and anti tumor effects of ellipticine derivatives on mouse l 1210 leukemia



Comparative cyto toxic and anti tumor effects of ellipticine derivatives on mouse l 1210 leukemia



Chemico-Biological Interactions 25(1): 45-58



Derivatives (12) of the antitumor alkaloid ellipticine (E) and ellipticinium were assayed in vitro on cultured L1210 cells. These drugs possess varying abilities to decrease the cell growth rate in a 1- to 1000-fold range. Some of them have a highly cytotoxic effect in the 10-8 to 10-6 M range. Non-specific intracellular damage is produced: multilobation of the nuclei, occurrence of numerous lipid granules, diminution of the size and increase in the number of mitochondrial profiles and several modifications of the internal architecture of mitochondria. 2-Methyl-9-hydroxyellipticinium (2-CH3-9-OHE) was submitted to a bioassay; it inactivates the tumorigenic potency of the cells exposed to it, when they are grafted back into mice in the same dose range which reduces in vitro the growth rate of the cells. A fairly good correlation holds between the in vitro and in vivo (antitumor effect) assays, offering a possible prescreening test for a cheaper and rapid evaluation of chemotherapeutic activity of these compounds. The results stress again the importance of the 9-hydroxy substitution in these series for improving the anticancer efficiency. The nature of the biochemical target of E and derivatives is discussed according to the data.

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Accession: 004993133

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PMID: 466727



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