Activity of a trinuclear platinum complex in human ovarian cancer cell lines sensitive and resistant to cisplatin: cytotoxicity and induction and gene-specific repair of DNA lesions

Colella, Gennaro; Pennati, Marzia; Bearzatto, A.; Leone, Roberto; Colangelo, Donato; Manzotti, C.; Daidone, Maria Grazia; Zaffaroni, Nadia

doi:10.1054/bjoc.2001.1751

Cited by 29 publications

(19 citation statements)

References 7 publications

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“…The A2780 and A2780cis cell lines have been well studied as models for measuring platinum drug cytotoxicity, although the conditions under which the assays have been conducted vary substantially; incubation times range between 48 and 96 h, with an initial plating of 1000-10,000 cells per well, and a variety of substrates in the medium [31][32][33][34][35][36].…”

Section: Cytotoxicitymentioning

confidence: 99%

Side-on binding of p-sulphonatocalix[4]arene to the dinuclear platinum complex trans-[{PtCl(NH3)2}2μ-dpzm]2+ and its implications for anticancer drug delivery

Wheate

Abbott

Tate

et al. 2009

Journal of Inorganic Biochemistry

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Section: Cytotoxicitymentioning

confidence: 99%

Side-on binding of p-sulphonatocalix[4]arene to the dinuclear platinum complex trans-[{PtCl(NH3)2}2μ-dpzm]2+ and its implications for anticancer drug delivery

Wheate

Abbott

Tate

et al. 2009

Journal of Inorganic Biochemistry

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“…Interestingly the DNA-adducts of BBR3464 and its dinuclear analogues are poorly recognized by the HMG1-proteins, which are well known to shield the cisplatin-induced DNA lesions from the nucleotide excision repair enzymes and thus to mediate to a great extend the cytotoxic effects of conventional platinum agents [53,56]. Moreover, despite the efficient removal of BBR-3464 adducts from the NER enzymes, this agent retain high cytotoxic activity against malignant cells with NER overexpression [57]. The most interesting feature of BBR3464, however, is its profound efficacy in different tumor models with a mutant p53 gene [13].…”

Section: Platinum Complexes With Trans-geometrymentioning

confidence: 99%

Novel Approaches Towards Development of Non-Classical Platinum-Based Antineoplastic Agents: Design of Platinum Complexes Characterized by an Alternative DNA-Binding Pattern and/or Tumor-Targeted Cytotoxicity

Momekov¹,

Bakalova²,

Karaivanova

2005

CMC

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Cisplatin is an essential antineoplastic agent whose introduction in clinical use revolutionized the treatment of several solid malignancies, especially those of germinative origin. The unfavorable toxicological profile of this drug, however as well as the resistance of some common malignancies solicited the search of platinum complexes, characterized by lower toxicity and/or broader antitumor spectrum. Thus during the last three decades a plethora of several thousand platinum coordination compounds have been synthesized and evaluated as potential antineoplastic agents. Despite of the numerous compounds investigated however only few of the proved to be of clinical significance and actually none of them could be considered as an ideal substitute for cisplatin regarding both lower toxicity and broader spectrum of anticancer activity. To a great extent the platinum-based drug discovery was confined at structural modification of the parent compound in line with the classic structure-activity relationship concept. Conversely, since the majority of platinum complexes developed so far are closely related structural analogues of cisplatin, it is not surprising that they produce similar cellular effects and any altered pattern of antitumor activity and/or toxicity is likely to be due to pharmacokinetic, rather than truly mechanistic, factors. Studies over the last few years have shown that the structural resemblance to cisplatin is not an absolute requirement for cytotoxicity, which broadens the search for cisplatin analogues towards non-classical compounds with prominent structural/pharmacodynamic dissimilarity to the prototype. This review covers the major approaches to elaboration of non-classical platinum complexes with emphasis on complexes interacting with DNA in a cisplatin-dissimilar fashion and complexes with tumor-targeted cytotoxicity.

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“…BBR3005, BBR3464, BBR3571, BBR3610 and BBR3611 (Fig. 2) have shown excellent in vitro activity in many cell lines including ovarian carcinomas [49], neuroblastomas [49,69], osteocarcinomas [45], cervical cancers [45], SCLC and NSCLC cancers [45], prostrate cancers [45] and astrocytomas [69]. In a panel of 7 human tumour cell lines (4 melanoma and 3 ovarian) BBR3464 had an IC 50 of 0.6 µM which was approximately 50-fold lower than the IC 50 for cisplatin (27.8 µM) [52].…”

Section: In Vitro Studiesmentioning

confidence: 99%

Multi-Nuclear Platinum Drugs: A New Paradigm in Chemotherapy

Wheate¹,

Jg²

2005

CMCACA

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The initial report of the therapeutic anticancer properties of a di-nuclear platinum complex in 1988 started a new paradigm in platinum based chemotherapy. Several multi-nuclear platinum complexes have entered clinical trials in recent years, with varying results. This group of charged complexes, consisting of di- and tri-nuclear compounds linked by aliphatic ligands, many with hydrogen bonding functionality, are able to overcome cisplatin and carboplatin resistance in many important human cancer cell lines. The adducts they form with DNA--which are, to some extent, affected by their pre-covalent association--are the reason for their increased cytotoxicity, and are distinctly different from those formed by cisplatin. Multi-nuclear platinum DNA adducts are broadly defined as flexible, non-directional and mainly interstrand cross-links. These complexes are also able to induce conformational changes in DNA, particularly the conversion from B-type to Z- and A-type. While these complexes are much more cytotoxic than cisplatin, they are also highly toxic. The maximum tolerated doses range from 0.006 to 1.1 mg/m(2) which is 10 to 100 fold lower than cisplatin. BBR3464 has shown in vivo activity at its MTD in several pre-clinical and clinical trials; however, recent phase II trials have shown that BBR3464, and other multi-nuclear platinum drugs, did not yield results substantially different from cisplatin, possibly due to their binding and degradation by human plasma proteins. This review will look at the success, and limitations, of multi-nuclear platinum drugs, and discuss their future potential as anti-cancer agents.

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Activity of a trinuclear platinum complex in human ovarian cancer cell lines sensitive and resistant to cisplatin: cytotoxicity and induction and gene-specific repair of DNA lesions

Cited by 29 publications

References 7 publications

Side-on binding of p-sulphonatocalix[4]arene to the dinuclear platinum complex trans-[{PtCl(NH3)2}2μ-dpzm]2+ and its implications for anticancer drug delivery

Side-on binding of p-sulphonatocalix[4]arene to the dinuclear platinum complex trans-[{PtCl(NH3)2}2μ-dpzm]2+ and its implications for anticancer drug delivery

Novel Approaches Towards Development of Non-Classical Platinum-Based Antineoplastic Agents: Design of Platinum Complexes Characterized by an Alternative DNA-Binding Pattern and/or Tumor-Targeted Cytotoxicity

Multi-Nuclear Platinum Drugs: A New Paradigm in Chemotherapy

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