Neocarzinostatin (NCS), an antitumor antibiotic, was found to inhibit cap formation of mouse lymphocytes and Raji cells. A treatment of lymphocytes with NCS in concentrations as low as 0.25 µg/ml is sufficient to cause a strong inhibition of ligand-independent cap formation. Compared to lymphocytes, Raji cells are less sensitive to the effect of NCS. The effect of NCS on cap formation could not be attributed to growth inhibition induced by the drug, for the inhibition of cap formation is induced readily and was detected even with resting cells such as lymphocytes. Inhibitors of DNA synthesis such as bleomycin, mitomycin C, and 1-β-d-arabinofuranosylcytosine showed no inhibitory effect on cap formation. Moreover, neither a RNA synthesis inhibitor nor a protein synthesis inhibitor affected the inhibitory action of NCS, suggesting that the principal target of NCS that caused the inhibition of cap formation is not DNA. Inasmuch as the systems of cap formation used in the present study do not require the function of microtubules, the inhibitory effect of NCS on cap formation could not be accounted for by the effect on microtubules. An active transport, uptake of 2-deoxy-glucose, is not affected by NCS but is completely inhibited by azide. This fact suggests that cellular metabolisms required for cap formation are not depressed by NCS. Although NCS, unlike cytochalasin B, does not induce rounding up of fibroblasts spread over a substrate, both drugs induced disappearance of membrane ruffles of these cells. From these results and those previously reported, the mode of action of NCS on the membrane-cytoskeletal (microtubules and microfilaments) system is discussed.

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This investigation was supported in part by Grants from the Ministry of Education, Science and Culture and the Ministry of Health and Welfare of Japan and by the Naito Research Grant (1978).

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