A study on direct antitumor activity of bropirimine (oral interferon inducer) for renal cell carcinoma.
Aryl pyrimidinones, including bropirimine, exert anti-tumor activity through the induction of interferon (IFN)-alpha. Herein, the direct anti-tumor effect of bropirimine on 17 renal cell carcinoma (RCC) surgically obtained was examined using an organ culture system closely resembling the in vivo state, and also using the heterotransplanted nude mouse system. The findings obtained using the organ culture system showed that bropirimine inhibited 3H-thymidine uptake significantly in 15 of the 17 RCC (88.2%) compared with the control. Furthermore, the 3H-thymidine uptake was dose-dependently inhibited in 3 of the 17 tumors (17.6%). The oral administration of bropirimine against RCC heterotransplanted in nude mice (JRC 901: an erythropoietin-producing strain) tended to inhibit tumor growth dose-dependently, but not significantly (mean tumor weight ratio: T/C ratio: over 43%, degeneration degree of tumor: incomplete). However, the production of erythropoietin from the JRC 901 was significantly inhibited. These findings suggest that bropirimine has a direct anti-tumor activity, without the mediation of IFN-alpha induction, against human renal cell carcinoma.
Onishi
T
T
Department of Urology, Jikei University School of Medicine.
Machida
T
T
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000473:pathology* / Q000628:therapy; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007369:Interferon Inducers / Q000008:administration & dosage / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000473:pathology* / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009924:Organ Culture Techniques
D000970:Antineoplastic Agents; D007369:Interferon Inducers; D003596:Cytosine; C033560:bropirimine