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Journal of Cancer Research and Clinical Oncology

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01.03.2007 | Original Paper

Platinum(II) complexes interfering with testicular steroid biosynthesis: drugs for the therapy of advanced or recurrent prostate cancers? Preclinical studies

verfasst von: Sabine Schertl, Rolf W. Hartmann, Christine Batzl-Hartmann, Thilo Spruß, Anton Maucher, Erwin von Angerer, Claus D. Schiller, Martin R. Schneider, Ronald Gust, Helmut Schönenberger

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 3/2007

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Abstract

[Meso-1,2-bis(2,6-dihalo-3/4-hydroxyphenyl)ethylenediamine]platinum(II) complexes (meso-1-PtLL′: 2,6-F₂,3-OH; meso-2-PtLL′: 2,6-F₂,4-OH; meso-3-PtLL′: 2,6-Cl₂,3-OH; meso-4-PtLL′: 2,6-Cl₂,4-OH; L = OH₂, L′ = OSO₃ or L,L′ = Cl₂) were designed with the aim to get drugs comprising both cytotoxic and testosterone level lowering potencies. It is assumed that such compounds are more efficient than the established endocrine therapeutic measures and can affect the development of hormone refractory prostate cancer (PC). With exception of meso-3-PtLL′ all Pt-complexes and the comparison compound cisplatin significantly reduced the testosterone level in experiments on male rats. However, in the test on the Dunning R3327 PC of the rat only cisplatin and meso-4-PtLL′ showed a significant anti-tumor activity at well-tolerated dose ranges. Meso-4-PtLL′ also significantly extended the time to disease progression in comparison with orchiectomy in this tumor model. Interestingly, the relapsed tumor, too, responded to meso-4-PtLL′ as demonstrated in a long-term study on orchiectomized rats bearing Dunning R3327 PC grafts. This effect cannot be ascribed to cytotoxic effects of meso-4-PtLL′ because of its inactivity on the human LNCaP/FGC PC cell line. Therefore, the contribution of an additional mechanism to the anti-prostate cancer activity of meso-4-PtLL′, presumably owing to its estrogenic potency, must be considered. This assumption was supported by test results with diethylstilbestrol (DES) (non-steroidal estrogen) on the Dunning R3327 PC of the rat relapsed after orchiectomy. This tumor model was strongly inhibited by DES. The possible mode of action of meso-4-PtLL′ is thoroughly discussed.

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Titel: Platinum(II) complexes interfering with testicular steroid biosynthesis: drugs for the therapy of advanced or recurrent prostate cancers? Preclinical studies
verfasst von: Sabine Schertl
Rolf W. Hartmann
Christine Batzl-Hartmann
Thilo Spruß
Anton Maucher
Erwin von Angerer
Claus D. Schiller
Martin R. Schneider
Ronald Gust
Helmut Schönenberger
Publikationsdatum: 01.03.2007
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 3/2007
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-006-0151-3

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Springer Medizin

Platinum(II) complexes interfering with testicular steroid biosynthesis: drugs for the therapy of advanced or recurrent prostate cancers? Preclinical studies

Abstract

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Springer Medizin

Abstract

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