Mode of action of estra-1,3,5(10)-triene-3,17 beta-diol 3-benzoate 17-[4-(4-bis(2-chloroethyl)amino)phenyl)-1-oxobutoxy)acet ate) on human breast carcinoma xenografts in nude mice.
To elucidate the mode of action of busramustine (KM2210), 17 beta- and alpha-busramustine, estradiol and chlorambucil were used for experimental chemo- and endocrino-therapy against hormone-dependent (T-61) and independent (MX-1) human breast carcinomas serially transplanted into BALB/cA female nude mice. Busramustine was administered po daily for 3 weeks at doses of 12.5-300 mg/kg for the beta-isomer and 25-300 mg/kg for the alpha-isomer. Five to 50 mg of estradiol per kg was administered im once, and 3 to 6 mg of chlorambucil per kg was administered po daily for 3 weeks. All of the compounds were effective against estrogen receptor-positive T-61 with a clear dose-response relationship, while estrogen receptor-negative MX-1 was sensitive to all of the agents except estradiol. Since the alpha-isomer of busramustine was effective against both tumor lines, the mode of action of 17 beta-busramustine may not be related to estrogenic action by estradiol released from the maternal compound. However, 17 beta-busramustine generated the estrogen receptor system of T-61 tumor and resulted in the endometrial hyperplasia of tumor-bearing nude mice, suggesting that this compound also has estrogenic action on transplanted human breast carcinoma and tumor-bearing host mice, besides non-estrogenic antitumor activity on human breast carcinoma xenografts.
Kubota
T
T
Department of Surgery, School of Medicine, Keio University, Tokyo.
Koh
J
J
Yamada
Y
Y
Oka
S
S
Enomoto
K
K
Ishibiki
K
K
Abe
O
O
Masui
O
O
Asano
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002699:Chlorambucil / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009929:Organ Size / Q000187:drug effects; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D002699:Chlorambucil; D004958:Estradiol; C036613:bestrabucil