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.

Abstract

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.

• Authors: T Kubota, J Koh, Y Yamada, S Oka, K Enomoto, K Ishibiki, O Abe, O Masui, K Asano
• Journal: Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 79 Issue 11 Pg. 1224-9 (Nov 1988) ISSN: 0910-5050 [Print] Japan
• PMID: 3147278 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Receptors, Estrogen
• Receptors, Progesterone
• Chlorambucil
• Estradiol
• bestrabucil

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Chlorambucil (analogs & derivatives, pharmacology, therapeutic use)
• Estradiol (analogs & derivatives, pharmacology, therapeutic use)
• Female
• Humans
• Mammary Neoplasms, Experimental (drug therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• Organ Size (drug effects)
• Receptors, Estrogen (analysis)
• Receptors, Progesterone (analysis)
• Transplantation, Heterologous