Platinum(IV) complex with adamantylamine overcomes intrinsic resistance to cisplatin in ovarian cancer cells

Horváth, Viktor; Blanářová, Olga Vondálová; Šindlerová, Lenka; Souček, Karel; Hofmanová, Jiřina; Sova, Petr; Kroutil, Aleš; Fedoročko, Peter; Kozubı́k, Alois

doi:10.1016/j.ygyno.2005.11.016

Cited by 28 publications

(25 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such effects were previously described in SK-OV-3 human ovarian cancer cells lacking p53 [33]. LA-12 was effective in killing these cells and was also able to overcome intrinsic cisplatin resistance in these cells.…”

Section: Discussionsupporting

confidence: 67%

The effect of cellular environment and p53 status on the mode of action of the platinum derivative LA-12

Roubalová

Kvardová²,

Hrstka³

et al. 2009

Invest New Drugs

Self Cite

View full text Add to dashboard Cite

In this study, we characterized the effects of LA-12 on tumor cell lines possessing wild type p53 and on p53-deficient/mutant cell lines and the results were compared to those obtained using cisplatin. We have determined changes of p53 levels, of its transcriptional activity, of its posttranscriptional modifications and the effect of the treatment on the cell cycle, on the induction of apoptosis and on gene expression. LA-12 induces weak accumulation of both transcriptionally active p53 tumor suppressor and of p21(WAF1/CIP1) protein. LA-12 and cisplatin also significantly differ in their effects on apoptosis and cell cycle and on gene expression spectra in studied cell lines. LA-12 induces higher apoptosis levels in comparison with those induced by cisplatin, especially in p53-deficient H1299 cells and in MCF-7DD cells with transcriptionally inactive p53. We suggest that LA-12-mediated apoptosis is not fully dependent on p53. This confirms the therapeutic potential of LA-12 as a more potent cytostatic agent for both tumor cells expressing wild type p53 and for p53-deficient or mutant cells.

show abstract

Section: Discussionsupporting

confidence: 67%

The effect of cellular environment and p53 status on the mode of action of the platinum derivative LA-12

Roubalová

Kvardová²,

Hrstka³

et al. 2009

Invest New Drugs

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the other hand, LA-12 treatment of A2780 cells still led to a permanent S phase arrest, which lasted at least until 72 h of treatment (unpublished results). Our previous results concerning cell cycle modulation of several ovarian (A2780, A2780cis, SK-OV-3) and colon cancer (HT-29) cell lines suggest that LA-12 typically induces a permanent S phase arrest [10,11], which may be the consequence of DNA damage [12].…”

Section: Discussionmentioning

confidence: 96%

“…It has shown a higher cytotoxicity than JM216 and no crossresistance with cisplatin, when tested on a panel of 14 cancer cell lines of various origin and different cisplatin sensitivity [9]. LA-12 has been found to be significantly more efficient than cisplatin in A2780 (parent, cisplatin sensitive), A2780cis (with acquired cisplatin resistance) or SK-OV-3 (with intrinsic cisplatin resistance) ovarian cancer cell lines, suggesting that it is able to overcome both acquired and intrinsic cisplatin resistance [10,11]. LA-12 demonstrated a higher hydrophobicity than cisplatin estimated by HPLC [9], and a higher cellular uptake in comparison with cisplatin in A2780 and A2780cis ovarian cancer cell lines [12].…”

mentioning

confidence: 99%

Different cell cycle modulation following treatment of human ovarian carcinoma cells with a new platinum(IV) complex vs cisplatin

Horváth

Souček²,

Šindlerová³

et al. 2007

Invest New Drugs

Self Cite

View full text Add to dashboard Cite

Platinum (IV) derivative with adamantylamine-LA-12-represents a new generation of highly efficient anti-cancer drug derived from cisplatin and is currently in the final stage of phase I clinical trials. Understanding the specific mechanisms of its effects on cell cycle is necessary for defining the mode of action of LA-12. In this study, we characterized the ability of LA-12 to induce cell cycle perturbations in ovarian cancer cell line A2780 as compared to equitoxic cisplatin treatment. LA-12 induced a permanent accumulation of A2780 cells in S phase while cisplatin caused G2/M arrest at 24-h time point, where we also detected an increased expression of Gadd45alpha protein. Although both derivatives induced a rapid increase of p53 expression, this was not associated with a down-regulation of Mdm2 protein. Increased expression of p21(Cip1/WAF1) protein and its association with cyclins A and B1 suggested that this cyclin-dependent kinase inhibitor might contribute significantly to the observed perturbations of cell cycle. The results of this study provide insight into the mechanism of action of platinum-based derivative with adamantylamine on cell cycle in ovarian cancer cells. The differences between effects of LA-12 and cisplatin suggest that more attention should be paid to elucidation of modes of action of novel platinum(IV) complexes at cellular level.

show abstract

“…Satraplatin is characterized by a comfort drug use (can be used orally) for patient unlike other Pt(II) drugs that can only be used intravenously. The presence of intracellular agents as glutathione, ascorbic acid and others is required for reduction of satraplatin and therefore for its activation (41). Also satraplatin can be used for treatment of prostate, lung and ovarian tumors with little signs of nephro-, neuro-and ototoxicity.…”

Section: R 2 Eddatype Ligandmentioning

confidence: 99%

Platinum Complexes with Edda (Ethylenediamine -N, N - Diacetate) Ligands as Potential Anticancer Agents

Jurišević

Radosavljević

Arsenijević

et al. 2016

Serbian Journal of Experimental and Clinical Research

View full text Add to dashboard Cite

show abstract

Platinum(IV) complex with adamantylamine overcomes intrinsic resistance to cisplatin in ovarian cancer cells

Cited by 28 publications

References 24 publications

The effect of cellular environment and p53 status on the mode of action of the platinum derivative LA-12

The effect of cellular environment and p53 status on the mode of action of the platinum derivative LA-12

Different cell cycle modulation following treatment of human ovarian carcinoma cells with a new platinum(IV) complex vs cisplatin

Platinum Complexes with Edda (Ethylenediamine -N, N - Diacetate) Ligands as Potential Anticancer Agents

Contact Info

Product

Resources

About