Cytotoxicity of lonidamine alone and in combination with other drugs against murine RIF-1 and human HT1080 cells in vitro.

细胞毒性 顺铂 药理学 丝裂霉素C 依托泊苷 细胞毒性T细胞 博莱霉素 阿霉素 毒性 纤维肉瘤 化学 体外 生物 化疗 生物化学 有机化学 遗传学
作者
S C Ning,George M. Hahn
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期刊:PubMed 卷期号:50 (24): 7867-70 被引量:17
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Lonidamine is an agent that is reported to inhibit recovery from potentially lethal damage. By itself, it has only mild anticancer activity. We have examined the ability of lonidamine to enhance the cytotoxicity of several drugs against a mouse and a human fibrosarcoma cell line in vitro. By itself, lonidamine showed only a limited cytotoxic effect with drug exposure up to 100 micrograms/ml and 24-h duration. Lower concentrations and shorter term exposures were not toxic to either of these tumor cell lines. When tested against the mouse line, the cytotoxicity of 5-fluorouracil, methotrexate, and etoposide was enhanced by lonidamine if the latter drug was given either before or after the exposure of the cells to the cytotoxic agents. For cisplatinum, bleomycin, mitomycin C, doxorubicin, and Actinomycin D, cytotoxicity was also enhanced, but only if lonidamine followed the other agents. In contrast, potentiation of 1,3-bis(2-chloroethyl)-1-nitrosourea toxicity was maximum when lonidamine preceded the nitrosourea. The human cells were more resistant to lonidamine and to the combination treatments than were the mouse cells. Nevertheless, substantial enhancement was seen particularly for cisplatin and mitomycin C. We examined in more detail the enhancement of cisplatin. Maximum interaction was obtained when lonidamine was given immediately following (or in conjunction with) the platinum agent. Our results suggest that lonidamine enhances the effects of several other agents in a time- and concentration-dependent manner and indicate a potential usefulness for lonidamine in multidrug therapy.

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