[Cross-resistance of HO-221 and various antitumor agents in sublines of mouse leukemia].

Abstract

HO-221, N-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2- nitrobenzoyl) urea is a new benzoylphenylurea derivative. The compound exhibits significant antitumor effects against various animal tumors, and was especially effective against the solid tumors implanted subcutaneously. HO-221 inhibits DNA polymerase alpha activity strongly in vitro. In this study, we examined the cross-resistance of HO-221 to various antitumor agents using sublines of mouse leukemia. HO-221 showed antitumor effects in mice bearing L 1210 or P 388 leukemia resistant to 10 antitumor agents, DM (daunomycin), MMC (mitomycin C), CDDP (cisplatin), 5-FU (5-fluorouracil), Ara-C (cytosine arabinoside), MTX (methotrexate), CPA (cyclophosphamide), CQ (carboquone), ADM (adriamycin) and VCR (vincristine), respectively. These antitumor agents were also effective in P 388 leukemia resistant to HO-221 (P 388/HO-221). Furthermore, CDDP- and MMC-resistant sublines showed a collateral sensitivity to HO-221 in vivo. The grow the inhibitory effects were also noted in vitro in ADM-, CDDP- and MMC-resistant cells by HO-221. However, the in vitro experiments didn't show such collateral sensitivity on the resistant sublines. These results suggest that there is no cross-resistance between HO-221 and other known antitumor agents, and that HO-221 seemed to be worth for evaluating clinical usefulness.

• Authors: T Nakajima, H Masuda, T Okamoto, M Watanabe, K Yokoyama, N Yamada, S Fujimoto, S Tsukagoshi, T Taguchi
• Journal: Gan to kagaku ryoho. Cancer & chemotherapy (Gan To Kagaku Ryoho) Vol. 18 Issue 2 Pg. 201-9 (Feb 1991) ISSN: 0385-0684 [Print] Japan
• PMID: 1899547 (Publication Type: English Abstract, Journal Article)

Chemical References

• Antineoplastic Agents
• Benzamides
• Mitomycins
• Nitrobenzenes
• N-(4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl)-N'-(2-nitrobenzoyl)urea
• Mitomycin
• Doxorubicin
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Benzamides (pharmacology)
• Cisplatin (pharmacology)
• Doxorubicin (pharmacology)
• Drug Resistance
• Leukemia L1210 (drug therapy, pathology)
• Leukemia P388 (drug therapy, pathology)
• Leukemia, Experimental (drug therapy, pathology)
• Mice
• Mitomycin
• Mitomycins (pharmacology)
• Nitrobenzenes (pharmacology)
• Tumor Cells, Cultured (drug effects)