A Fluorine-containing Anthracycline (ME2303) as a New Antitumor Agent against Murine and Human Tumors and Their Multidrug-resistant Sublines

Takashi Tsuruo, Keisuke Yusa, Yojiro Sudo, Riko Takamori, Yoshikazu Sugimoto

研究成果: Article査読

27 被引用数 (Scopus)

抄録

A new fluorine-containing anthracycline derivative, ME2303, showed excellent antitumor activity against various experimental tumor models. The i.p. or i.v. administrations of ME2303 on Day 1 or on Days 1, 5, and 9 against i.p.-implanted LI 210 leukemia cells rendered more than 50% of mice tumor free at wide ranges of nontoxic doses, whereas the incidence of cure obtained with Adriamycin (ADM) was less than that obtained with ME2303. ME2303 given i.p. or i.v. on Day 1 or Days 1, 5, and 9 was also effective against i.p.-implanted P388 leukemia ceils, and higher incidences of cure were obtained than with ADM. ME2303 administered i.v. on Days 1, 8, 15, and 22 showed prominent antitumor activity against s.c.-implanted colon adenocarcinomas 26 and 38, Lewis lung carcinoma, B16 melanoma, and M5076 sarcoma. Against colon adenocarcinoma 26, ME2303 induced cure in 16 of 20 mice at doses of 35 to 71 μmol/kg, whereas no cure was observed with ADM. Significant growth inhibition of colon adenocarcinoma 38, Lewis lung carcinoma, B16 melanoma, and M5076 sarcoma cell lines was also observed at a dose of 18 to 106 μmol/ kg. ME2303 was effective against human and murine multidrug-resistant cells in vitro. For example, human myelogenous leukemia K562 resistant to ADM (K562/ADM) was only 2.8-fold more resistant to ME2303, while the cells were 200-fold more resistant to ADM when the values for the concentration of drug required for 50% inhibition of cell growth were compared. ME2303 was also more effective than ADM against human leukemia CCRF-CEM resistant to vinblastine, human ovarian carcinoma A2780 resistant to ADM, human epidermoid carcinoma KB cells resistant to colchicine, and mouse leukemia P388 resistant to ADM and vincristine. Therapeutic effects were obtained in vivo against ADM- and, especially, vincristine-resistant P388 leukemia. ME2303 is one of the most interesting potential antitumor agents to be studied further.

本文言語English
ページ(範囲)5537-5542
ページ数6
ジャーナルCancer Research
49
20
出版ステータスPublished - 1989 10 15
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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