(NH3)2Pt(triacid) and (PPh3)2Pt(dehydrocholate)2 are novel bile acid-conjugated platinum complexes administered by oral route. The aims of the present study were to evaluate their in vitro cytotoxic activities on rat hepatoma cell line N1-S1, the in vivo antitumour effects in a syngeneic and orthotopic rat hepatoma model and the drug-related toxicities. Cisplatin, carboplatin and mitoxantrone were used as control drugs. In vitro experiments showed a concentration- and time-dependent antiproliferative activity of bile-conjugated platinum complexes. (NH3)2Pt(triacid) had similar effects on cell growth of cisplatin and carboplatin (e.g. at 48 h, IC50 0.7 ± 0.05 μM vs. 0.63 ± 0.28 μM and 1.1 ± 0.3 μM, respectively; mean ± S.D.). (NH3)2Pt(triacid) was able to inhibit tumour growth in a dose-dependent extent, reaching the maximum inhibitory effect at the 80 mg/kg dose (1.95 ± 0.5 g vs. 13.85 ± 3.9 g of control tumour weight). By contrast, despite the promising in vitro antiproliferative activity, (PPh3)2Pt(dehydrocholate)2 showed no significant in vivo antitumour effect. The toxicity profile of (NH3)2Pt(triacid) resulted favourable with minimal loss of weight and no gastrointestinal or neurological symptoms. Instead, (PPh3)2Pt(dehydrocholate)2 showed dose-dependent signs of severe weight loss and neurological alterations. In conclusion (NH3)2Pt(triacid) is a tolerable and active platinum derivative endowed by a preclinical antitumour activity by oral route. © 2006 Elsevier B.V. All rights reserved.

In vitro and in vivo antitumour effects of novel, orally active bile acid-conjugated platinum complexes on rat hepatoma / C. Barbara, P. Orlandi, G. Bocci, A. Fioravanti, A. DI PAOLO, G. Natale, M. DEL TACCA, R. Danesi. - In: EUROPEAN JOURNAL OF PHARMACOLOGY. - ISSN 0014-2999. - 549:1-3(2006 Nov 07), pp. 27-34. [10.1016/j.ejphar.2006.08.015]

In vitro and in vivo antitumour effects of novel, orally active bile acid-conjugated platinum complexes on rat hepatoma

R. Danesi
Ultimo
2006

Abstract

(NH3)2Pt(triacid) and (PPh3)2Pt(dehydrocholate)2 are novel bile acid-conjugated platinum complexes administered by oral route. The aims of the present study were to evaluate their in vitro cytotoxic activities on rat hepatoma cell line N1-S1, the in vivo antitumour effects in a syngeneic and orthotopic rat hepatoma model and the drug-related toxicities. Cisplatin, carboplatin and mitoxantrone were used as control drugs. In vitro experiments showed a concentration- and time-dependent antiproliferative activity of bile-conjugated platinum complexes. (NH3)2Pt(triacid) had similar effects on cell growth of cisplatin and carboplatin (e.g. at 48 h, IC50 0.7 ± 0.05 μM vs. 0.63 ± 0.28 μM and 1.1 ± 0.3 μM, respectively; mean ± S.D.). (NH3)2Pt(triacid) was able to inhibit tumour growth in a dose-dependent extent, reaching the maximum inhibitory effect at the 80 mg/kg dose (1.95 ± 0.5 g vs. 13.85 ± 3.9 g of control tumour weight). By contrast, despite the promising in vitro antiproliferative activity, (PPh3)2Pt(dehydrocholate)2 showed no significant in vivo antitumour effect. The toxicity profile of (NH3)2Pt(triacid) resulted favourable with minimal loss of weight and no gastrointestinal or neurological symptoms. Instead, (PPh3)2Pt(dehydrocholate)2 showed dose-dependent signs of severe weight loss and neurological alterations. In conclusion (NH3)2Pt(triacid) is a tolerable and active platinum derivative endowed by a preclinical antitumour activity by oral route. © 2006 Elsevier B.V. All rights reserved.
Bile acid; Carboplatin; Cisplatin; Hepatoma; Mitoxantrone; Platinum complex
Settore BIO/14 - Farmacologia
7-nov-2006
16-ago-2006
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1120716
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 21
  • ???jsp.display-item.citation.isi??? 17
social impact