Antitumor activities of IKP-104, a 4(1H)-pyrizinone derivative, on cultured and implanted tumors

Japanese Journal of Cancer Research : Gann
F MizuhashiI Tomita

Abstract

Antitumor activities of IKP-104, a 4(1H)-pyrizinone derivative, were investigated with cultured tumor cell lines and implanted tumors in mice. IKP-104 inhibited the growth of cultured murine tumor cell lines (L1210 leukemia, Lewis lung carcinoma and B16 melanoma) and human tumor cell lines (K562 leukemia and HeLa cervical carcinoma). It also had antitumor effects on implanted murine ascitic tumors (L1210 leukemia and sarcoma 180) and a murine solid tumor (Lewis lung carcinoma). IKP-104 could be classified as a phase-dependent cytostatic drug based on the mode of growth inhibition of cultured B16 melanoma cells compared with those of several other antitumor agents. The effect of IKP-104 on the cell cycle traverse of cultured B16 melanoma cells was estimated by morphological and flow cytometric analyses. Cells accumulated in the mitotic phase, and abortive mitosis or polyploidy or multinucleation was induced from 6 h after exposure to IKP-104. Based on these results, IKP-104 is expected to be useful for the treatment of tumors, and its mode of action seemed to be similar to that of metaphase arrestants such as colchicine or vinca alkaloids.

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