Comparative in vitro and in vivo pharmacological investigation of platinum(IV) complexes as novel anticancer drug candidates for oral application

Theiner, Sarah; Varbanov, Hristo P.; Galanski, Markus; Egger, Alexander; Berger, Walter; Heffeter, Petra; Keppler, Bernhard K.

doi:10.1007/s00775-014-1214-6

Cited by 52 publications

(51 citation statements)

References 40 publications

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“…Tissue Pt accumulation was also detected by ICP-MS as previously described [66]. 0.1 g tissue samples from nude mice were dried overnight in a clean oven at 65°C.…”

Section: Methodsmentioning

confidence: 99%

NEAT1 upregulates EGCG-induced CTR1 to enhance cisplatin sensitivity in lung cancer cells

et al. 2016

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Platinum-based drugs are the firstline of treatment for non-small cell lung cancer (NSCLC), but resistance to these drugs is a major obstacle to effective chemotherapy. Our previous study revealed that the green tea polyphenol, EGCG, induced cisplatin transporter CTR1 (copper transporter 1) and enhanced cisplatin sensitivity in ovarian cancer. In this study, we found that EGCG upregulated CTR1 and increased platinum accumulation in NSCLC (A549, H460 and H1299) cells, cDDP-resistant A549 cells and a nude mouse xenograft model. Cisplatin-induced inhibition of cell growth was enhanced by EGCG treatment in vitro and in vivo. MicroRNA hsa-mir-98-5p appears to suppress CTR1 gene expression, while long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) appears to enhance it. Bioinformatics analysis showed that hsa-mir-98-5p has specific complementary binding sites for NEAT1. In addition, hsa-mir-98-5p was predicted to be a putative CTR1 target. NEAT1 may act as a competing endogenous lncRNA to upregulate EGCG-induced CTR1 by sponging hsa-mir-98-5p in NSCLC. Our findings reveal a novel mechanism how NEAT1 upregulates EGCG-induced CTR1 and enhances cisplatin sensitivity in vitro and in vivo, and suggest EGCG could serve as an effective adjuvant chemotherapeutic in lung cancer treatment.

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“…Tissue Pt accumulation was also detected by ICP-MS as previously described [66]. 0.1 g tissue samples from nude mice were dried overnight in a clean oven at 65°C.…”

Section: Methodsmentioning

confidence: 99%

NEAT1 upregulates EGCG-induced CTR1 to enhance cisplatin sensitivity in lung cancer cells

et al. 2016

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“…Encouraged by the clinical results of satraplatin, various Pt (IV) complexes without bioactive axial ligands were synthesized and evaluated (Fig. ) . Although various small‐molecule Pt (IV) complexes are emerging, most studies had only been carried out at the cellular level until now, including cytotoxicity, cellular uptake, and mechanisms of anticancer activity, and there was no further systematic animal study about in vivo pharmacokinetic and pharmacodynamic profiles.…”

Section: Platinum (Iv) Complex‐based Delivery Systemsmentioning

confidence: 99%

“…It should be noted that high cytotoxicity in vitro does not ensure desirable anticancer effect in vivo. For instance, although compared with compound 4b, compound 4a was more effective against CH1, SW480, and A549 cell lines in vitro, in CT‐26 cells xenograft mice model, the in vivo anticancer effect of compound 4a was similar to that of compound 4b …”

Section: Platinum (Iv) Complex‐based Delivery Systemsmentioning

confidence: 99%

“…For instance, although compared with compound 4b, compound 4a was more effective against CH1, SW480, and A549 cell lines in vitro, in CT-26 cells xenograft mice model, the in vivo anticancer effect of compound 4a was similar to that of compound 4b. 107 Among these complexes, LA-12 ((OC-6-43)-bus (acetate) (1-adamantylamine) amminedichloroplatinum (IV), compound 6a), a homologous compound of satraplatin was one of most promising drugs to come into clinical studies. Compared to satraplatin, LA-12 contained 1-adamantylamine as nonleaving ligand rather than cyclohexylamine, and LA-12 was proved to be more effective than satraplatin in nude mice bearing human tumor xenografts.…”

Section: -91mentioning

confidence: 99%

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Recent Advances in Platinum (IV) Complex‐Based Delivery Systems to Improve Platinum (II) Anticancer Therapy

Han

Sun

Wang

et al. 2015

Medicinal Research Reviews

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Cisplatin and its platinum (Pt) (II) derivatives play a key role in the fight against various human cancers such as testicular, ovarian, head and neck, lung tumors. However, their application in clinic is limited due to dose- dependent toxicities and acquired drug resistances, which have prompted extensive research effort toward the development of more effective Pt (II) delivery strategies. The synthesis of Pt (IV) complex is one such an area of intense research fields, which involves their in vivo conversion into active Pt (II) molecules under the reducing intracellular environment, and has demonstrated encouraging preclinical and clinical outcomes. Compared with Pt (II) complexes, Pt (IV) complexes not only exhibit an increased stability and reduced side effects, but also facilitate the intravenous-to-oral switch in cancer chemotherapy. The overview briefly analyzes statuses of Pt (II) complex that are in clinical use, and then focuses on the development of Pt (IV) complexes. Finally, recent advances in Pt (IV) complexes in combination with nanocarriers are highlighted, addressing the shortcomings of Pt (IV) complexes, such as their instability in blood and irreversibly binding to plasma proteins and nonspecific distribution, and taking advantage of passive and active targeting effect to improve Pt (II) anticancer therapy.

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“…Overall, there is still a need to get to a more profound understanding of details governing Pt(II)-DNA interactions [24,25], including on seemingly trivial aspects such as the influence of small anions [26][27][28] on the activation of Pt antitumor drugs, or the influence of pH and buffer on the reaction with nucleotides and nucleic acids [24]. Given the numerous ''non-traditional" Pt antitumor drugs presently in development and novel concepts regarding their applications [29][30][31][32][33], questions on Pt(II)-DNA interactions will continue to be of considerable relevance.…”

Section: Introductionmentioning

confidence: 99%

(N7)-Platination and its effect on (N1)H-acidification in nucleoside phosphate derivatives

Sigel

Operschall

Griesser

et al. 2016

Inorganica Chimica Acta

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Comparative in vitro and in vivo pharmacological investigation of platinum(IV) complexes as novel anticancer drug candidates for oral application

Abstract: Abstract© SBIC 2014 petra.heffeter@meduniwien.ac.at. Electronic supplementary material The online version of this article

Cited by 52 publications

References 40 publications

NEAT1 upregulates EGCG-induced CTR1 to enhance cisplatin sensitivity in lung cancer cells

NEAT1 upregulates EGCG-induced CTR1 to enhance cisplatin sensitivity in lung cancer cells

Recent Advances in Platinum (IV) Complex‐Based Delivery Systems to Improve Platinum (II) Anticancer Therapy

(N7)-Platination and its effect on (N1)H-acidification in nucleoside phosphate derivatives

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