Abstract |
The novel cisplatin analogue D-17872 was studied for its anticancer activity using in vivo and in vitro preclinical models. The compound at the sublethal dose of 215 mg/kg (ca. 50% of the approximate LD50) induced no nephrotoxic effect strong enough to increase the blood urea level in rats. It had good in vivo antitumor efficacy against murine P388 (max. ILS: D-17872 132%, cisplatin 55%) and L1210 leukemia (max. ILS: D-17872 43%, cisplatin 38%), L5222 leukemia of the rat (max. ILS: D-17872 163%, cisplatin 163%) and murine B16 melanoma. Activity against P388 leukemia substantially exceeded that of cisplatin. Moreover, the M5076 reticulum cell sarcoma implanted into the subrenal capsule and the DMBA-induced mammary tumor of the rat were inhibited by D-17872 to a greater extent than by cisplatin (min. T/C: D-17872 -3%, cisplatin 11%). Using clonogenic microassays, D-17872 was active in vitro against a variety of human and rodent tumor cell lines, albeit at higher concentrations than cisplatin (IC50 values: D-17872 2.6-12.7 mumol/l, cisplatin 0.13-0.42 mumol/l). Apart from its cytotoxic action it was able to induce in vitro differentiation of the human HL-60 and K562 and of the murine M1-T22 cell lines, while cisplatin induced differentiation only in the HL-60 cell line. Thus D-17872 exhibited a pharmacological and toxicological profile different from that of the parent compound. The results suggest that induction of differentiation contributes to the antineoplastic efficacy of this novel cisplatin derivative.
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Authors | H R Maurer, C Echarti, R Voegeli, J Pohl, P Hilgard |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 32
Issue 2
Pg. 123-8
( 1993)
ISSN: 0344-5704 [Print] Germany |
PMID | 8485806
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- Ethylenediamines
- D 17872
- Cisplatin
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Cell Differentiation
(drug effects)
- Cell Division
(drug effects)
- Cisplatin
(administration & dosage, analogs & derivatives, pharmacology, therapeutic use)
- Erythrocytes
(drug effects)
- Ethylenediamines
(administration & dosage, pharmacology, therapeutic use)
- Female
- Injections, Intraperitoneal
- Male
- Mice
- Mice, Inbred C57BL
- Monocytes
(drug effects)
- Neoplasms, Experimental
(drug therapy, pathology)
- Rats
- Rats, Sprague-Dawley
- Tumor Cells, Cultured
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