[1,2-Bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] dichloro-platinum(II): an endocrine-active platinum complex with a specific prostatic tumor-inhibiting activity.
[1,2-Bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]dichloro-platinum (II), (C), a platinum complex with endocrine activity and a specific effect on hormone-dependent mammary tumors, was tested for its tumor-inhibitory activity in the hormone-sensitive R 3327 and Nb prostate carcinoma models of the rat and for its endocrine activities in comparison to the ligand L and diethylstilbestrol (DES). Established tumors of the R 3327 prostate tumor were strongly inhibited by C. Its effect equaled that of DES and was significantly better than that of L. Accessory sex organ weights and testosterone levels were strongly reduced by C as well as L. This antigonadotrophic effect, which is almost comparable to DES, was confirmed in 10 day experiments with intact, mature mice and rats, whereas a direct antiandrogenic activity was not given. A part of the antitumor action of C is therefore due to this antigonadotrophic activity. Affinities to estrogen, progesterone, and androgen receptors, however, were very low. The hormone-sensitive Noble Nb-R prostatic carcinoma was almost completely inhibited by C, whereas L had only a weak effect. As C has no significant effect on the hormone-independent R 3327 HI prostate tumor and as its effect on hormone-dependent tumors is significantly better than that of the ligand L in spite of their similar endocrine properties, an apparently specific antiproliferative effect of C only on hormone-dependent prostate tumors is obvious. This was further shown in a long-term experiment with the R 3327 prostate carcinoma. Whereas tumors in the castration group relapsed from androgen ablation and exerted a progressive tumor growth, therapy with C almost completely prevented this relapse phenomenon. After 25 weeks of treatment, C inhibited tumor growth by 90% compared to castration. Owing to these results, this new endocrine active platinum complex with an apparently specific effect on hormone-dependent prostate tumors can be of value for the therapy of the prostatic carcinoma.
Schneider
M R
MR
Institute of Pharmacy, University of Regensburg, Federal Republic of Germany.
Schiller
C D
CD
Humm
A
A
Spruss
T
T
Schönenberger
H
H
Amselgruber
W
W
Sinowatz
F
F
D000818:Animals; D000970:Antineoplastic Agents; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D004702:Endocrine Glands / Q000187:drug effects*; D008297:Male; D015394:Molecular Structure; D009929:Organ Size / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D012008:Recurrence; D013739:Testosterone / Q000378:metabolism
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011987:Receptors, Steroid; D013739:Testosterone; C042922:dichloro(1,2-bis(4-hydroxyphenyl)ethylenediamine)platinum II