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Reversal of Multidrug Resistance by Synthetic Isoprenoids in the KB Human Cancer Cell Line¹

Department of Biochemistry and Urology, Oita Medical School, Hazama-cho, Oita 879-56, Japan

A colchicine resistant clone, Ch^r-24, derived from the human carcinoma KB cell line is extensively resistant to multiple drugs including vinblastine, vincristine, Adriamycin, actinomycin D, and daunomycin. In comparison with KB cells, very low accumulation of daunomycin or vincristine is observed in multidrug-resistant cells. Two isoprenoids with 9 to 10 isoprene chains (polyprenoids), N-(p-methylbenzyl)decaprenylamine and N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine overcame the multidrug resistance almost completely in cultured Ch^r-24, whereas they only slightly sensitized the parental KB cells to anticancer agents. Both isoprenoids enhance the accumulation of vincristine or daunomycin in Ch^r-24, possibly by inhibiting efflux and also by enhancing influx of anticancer agents. A verapamil-like structure of N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine is discussed in relation to its ability to overcome drug resistance.

¹ This work was supported by a grant-in-aid for Cancer Research from the Ministry of Education, Science, and Culture of Japan.

² Present address: Central Research Laboratory, Nisshin Flour Milling Co., Saitama 354, Japan.

³ To whom requests for reprints should be addressed.

Received 6/18/85. Revised 12/ 9/85. Revised 3/27/86. Accepted 5/19/86.