Anti-metastatic and Anti-angiogenic Properties of Potential New Anti-cancer Drugs Based on Metal Complexes of Selenosemicarbazones

Zec, Manja; Srdiċ-Rajiċ, Tatjana; Konić-Ristić, Aleksandra; Todorović, Tamara R.; Andjelković, Katarina; Filipovic-Ljeskovic, Ivana; Radulović, Siniša

doi:10.2174/187152012803529682

Cited by 30 publications

(26 citation statements)

References 38 publications

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“…It is also concluded that angiogenesis inhibition ascribed to Pd 2 Spm/DTX combinations (in the CAM assay) can be partially endorsed to VEGFR2 tyrosine kinase activation, since the Pd 2 Spm/DTX IC 50 dosage caused only a 25% inhibition of the VEGFR2 pathway. Indeed, the antiangiogenic activity observed (due to the action of Pd 2 Spm/DTX) can also be explain by the ability of Pd to react with ROS (which have proangiogenic properties) reducing their accumulation in the cells, in a mechanism similar to that occurring with Ni-complex agents [38]. Another possibility lies on the fact that Pd(II) agent can target the cytoskeleton, mostly the microtubules on the cellular protein content and the cytoskeleton (previously reported by the authors [12]), and closely related to the prevention of formation of the tubular network needed for new vessel development [37].…”

Section: Discussionmentioning

confidence: 99%

Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent

et al. 2016

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The present work is aimed at evaluating the antitumour properties of a Pd(II) dinuclear complex with the biogenic polyamine spermine, by investigating: i) the anti-angiogenic and anti-migration properties of a Pd(II) dinuclear complex with spermine (Pd2Spm); ii) the anti-proliferative activity of Pd2Spm against a triple negative human breast carcinoma (MDA-MB-231); and finally iii) the putative interaction mediated by combination of Pd2Spm with Docetaxel. Anti-invasive (anti-angiogenic and anti-migratory) as well as anti-proliferative capacities were assessed, for different combination schemes and drug exposure times, using the CAM assay and VEGFR2 activity measurement, the MatrigelTM method and the SRB proliferation test. The results thus obtained evidence the ability of Pd2Spm to restrict angiogenesis and cell migration: Pd2Spm induced a marked inhibition of migration (43.8±12.2%), and a higher inhibition of angiogenesis (81.8±4.4% for total length values, at 4 μM) as compared to DTX at the clinical dosage 4x10-2 μM (26.4±14.4%; n = 4 to 11). Combination of Pd2Spm/DTX was more effective as anti-invasive and anti-proliferative than DTX or Pd2Spm in sole administration, which is compatible with the occurrence of synergism: for the anti-angiogenic effect, IC50(Pd2Spm/DTX) = 0.5/0.5x10-2 μM vs IC50(DTX) = 1.7x10-2 μM and IC50(Pd2Spm) = 1.6 μM. In conclusion, the reported effects of Pd2Spm on angiogenesis, migration and proliferation showed that this compound is a promising therapeutic agent against this type of breast cancer. Moreover, combined administration of Pd2Spm and DTX was found to trigger a substantial synergetic effect regarding angiogenesis inhibition as well as anti-migratory and anti-proliferative activities reinforcing the putative use of Pd(II) complexes in chemotherapeutic regimens. This is a significant outcome, aiming at the application of these combined strategies towards metastatic breast cancer (or other type of resistant cancers), justifying further studies that include pre-clinical trials.

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Section: Discussionmentioning

confidence: 99%

Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent

et al. 2016

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“…Their analogs, the selenosemicarbazones, were also reported to have similar effects on cancer cells [15, 16]. A series of novel selenosemicarbazones were synthesized in our laboratory and among these compounds, 2-24a (Figure 1A) complexed with Cu (2-24a/Cu) showed anti-cancer activity in cancer cells.…”

Section: Resultsmentioning

confidence: 99%

A selenosemicarbazone complex with copper efficiently down-regulates the 90-kDa heat shock protein HSP90AA1 and its client proteins in cancer cells

et al. 2014

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BackgroundThe 90-kDa heat shock protein HSP90AA1 is critical for the stability of several proteins that are important for tumor progression and thus, is a promising target for cancer therapy. Selenosemicarbazone metal complexes have been shown to possess anticancer activity through an unknown molecular mechanism.MethodsThe MTT assay, fluorescence-activated cell sorting, and fluorescent microscopy were used to analyze the mechanism of the anti-cancer activity of the selenosemicarbazone metal complexes. Additionally, RNA-seq was applied to identify transcriptional gene changes, and in turn, the signaling pathways involved in the process of 2-24a/Cu-induced cell death. Last, the expression of HSP90AA1, HSPA1A, PIM1, and AKT proteins in 2-24a/Cu-treated cells were investigated by western blot analysis.ResultsA novel selenosemicarbazone copper complex (2-24a/Cu) efficiently induced G2/M arrest and was cytotoxic in cancer cells. 2-24a/Cu significantly induced oxidative stress in cancer cells. Interestingly, although RNA-seq revealed that the transcription of HSP90AA1 was increased in 2-24a/Cu-treated cells, western blotting showed that the expression of HSP90AA1 protein was significantly decreased in these cells. Furthermore, down-regulation of HSP90AA1 led to the degradation of its client proteins (PIM1 and AKT1), which are also cancer therapy targets.ConclusionOur results showed that 2-24a/Cu efficiently generates oxidative stress and down-regulates HSP90AA1 and its client proteins (PIM1, AKT1) in U2os and HeLa cells. These results demonstrate the potential application of this novel copper complex in cancer therapy.

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“…Platelet-coated surfaces were prepared as described previously 16 with modifications for ex vivo testing. Suspensions of platelets (0.1 mL containing 1×10 8 platelets in HEPES Tyrode's buffer), isolated from the whole blood before and after intervention, were added to plastic flat-bottomed micro-titre wells.…”

Section: Determination Of Platelet-endothelial Cells Adhesion -Ex Vivomentioning

confidence: 99%

Biological activity of Aronia melanocarpa antioxidants pre-screening in intervention study design

Konić-Ristić

Srdiċ-Rajiċ

Kardum

et al. 2013

JSCS

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Beneficial effects of black chokeberry fruits and juices in health promotion and prevention of chronic diseases shown both in epidemiological and dietary intervention studies are often connected with their antioxidant activity. The aim of this study was to investigate the total phenolics and anthocyanins content, chemical antioxidant activity (DPPH-assay), antioxidant protection in erythrocytes and anti-platelet activity in vitro of three different chokeberry products: commercial and fresh pure chokeberry juice and crude lyophilized water-ethanol extract of chokeberry fruits, as a part of their pre-clinical evaluation. Obtained results indicated the differences in chemical composition and antioxidant activity of investigated products. Cellular effects, including both in vitro anti-platelet and antioxidant effects, were not directly correlated with the chemical antioxidant activity and results obtained in vitro for anti-platelet effects just partially consistent with the results obtained in vivo, in a pilot intervention trial. In conclusion, chemical analyses and in vitro experiments on foods and their bioactives are a valuable pre-screening tool for the evaluation of their biological activity. However, extrapolation of the obtained results to the in vivo settings is often limited and influenced by the bioavailability and metabolism of native dietary compounds or interactions with different molecules within the human body. [Projekat Ministarstva nauke Republike Srbije, br. III41030

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Anti-metastatic and Anti-angiogenic Properties of Potential New Anti-cancer Drugs Based on Metal Complexes of Selenosemicarbazones

Cited by 30 publications

References 38 publications

Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent

Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent

A selenosemicarbazone complex with copper efficiently down-regulates the 90-kDa heat shock protein HSP90AA1 and its client proteins in cancer cells

Biological activity of Aronia melanocarpa antioxidants pre-screening in intervention study design

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