Non-substituted N-heteroaromatic selenosemicarbazone metal complexes induce apoptosis in cancer cells via activation of mitochondrial pathway

Srdiċ-Rajiċ, Tatjana; Zec, Manja; Todorović, Tamara R.; Anđelković, Katarina; Radulović, Siniša

doi:10.1016/j.ejmech.2011.05.039

Cited by 36 publications

(28 citation statements)

References 60 publications

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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%

“…Selenium compounds can efficiently induce cell death in various cancer cells [14]. For example, metal complexes of selenosemicarbazones (selenium in the place of sulfur) induced apoptosis through the mitochondria pathway in cancer cells [15]. Additionally, nickel (II) complexes of selenosemicarbazones efficiently inhibited metastasis and angiogenesis in breast cancer cells [16].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

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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“…It is well known that commonly used anticancer drugs trigger apoptosis to kill cancer cells [3]. On the basis of New gold(III) compounds and apoptosis Bostancıoğlu et al 229 this idea, apoptotic effects of [Au(L)B](PF 6 ) 2 and [(Au(L) B)Pt]Cl 2 complexes were evaluated microscopically and biochemically in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the cytotoxicity of chemotherapeutics, resistance of chemotherapeutics results in the failure of cancer treatment. Primary or acquired resistance of many tumors has led researchers to focus on searching new and strong strategies to enhance the efficacy of chemotherapy [3]. Although cisplatin and carboplatin, which are well known and the most effective anticancer drugs, are used widely, their resistance as well as toxic effects on healthy tissue have led to a need to create more effective new metal complexes with less toxicity.…”

Section: Introductionmentioning

confidence: 99%

Gold(III) compounds-mediated inhibition of lung cancer cell proliferation

Bostancıoğlu

Kaya²,

Koparal³

et al. 2016

Anti-Cancer Drugs

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Research on chemotherapeutics for lung cancer is crucial for designing a new therapeutic strategy against malignant lung tumors. Although radiotherapy and chemotherapy, which are not selective for cancer cells and exert toxic effects on healthy cells, have a limited advantage, they are the primary treatment modalities for non-small lung cancer. In addition to cytotoxicity, resistance of chemotherapeutics results in failure of treatment. This is why it is of utmost importance to focus on the creation of new chemotherapeutics without toxicity for the successful treatment and improved survival of cancer patients. New gold(III) and Pt(II) compounds were synthesized with a heterocyclic ligand using 2-phenylimidazo[4,5-f][1,10]phenanthroline as a ligand and bis-1,4-di[([1,10] phenanthroline-5-il)amino]-2-buten as a bridge molecule. The characterization of the compounds was carried out using a variety of spectroscopic methods (H NMR, IR, MS, and elemental analysis). Their antiproliferative, antitumoral, and apoptotic activities were determined. IR spectra and NMR results confirmed the formation of dinuclear heterocyclic complexes for two metal complexes. Cytotoxicity studies on lung cancer cells (A549) and healthy cells (CHL) showed a marked increase in cytotoxicity with the use of gold(III) complexes, and especially [Au(L)B](PF6)2 showed higher cytotoxic and apoptotic features than cisplatin at lower concentrations in cancer cells. These findings have been supported by results from DAPI staining and colorimetric measurement of the caspase-3 enzyme in both cell lines. Compounds showed selective toxicity on the cancer cells. In the light of the high efficacy of our newly synthesized gold complexes, they might be good and promising anticancer agents compared with cisplatin.

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“…15 Previous investigations showed that selenosemicarbazone complexes exhibited strong dose-dependent cytotoxic activity against a panel of several human tumour cell lines, and this effect was comparable to that of cisplatin. [16][17][18][19] This study was undertaken with the aim to investigate the in vitro antioxidative potential of Ni(II), Cd(II) and Zn(II) selenosemicarbazone complexes. The analysis of the toxicity level of chemical compounds is one of the most important steps required for further biological studies.…”

Section: Introductionmentioning

confidence: 99%

High antioxidative potential and low toxic effects of selenosemicarbazone metal complexes

Dekanski¹,

Todorović

Mitić

et al. 2013

JSCS

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Novel metal-based compounds with therapeutic potential have become the subject of intense investigations in inorganic chemistry and biomedical science. Recently, strong dose-dependent cytotoxic activities of selenosemicarbazone metal complexes against several human cancer cell lines were demonstrated. The aim of the present study was to investigate in vitro antioxidative potential of Ni(II), Cd(II) and Zn(II) selenosemicarbazone complexes. All three investigated complexes exhibited high 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) radical cation (ABTS •+ ) scavenging capacity, comparable with ascorbic acid. In an acute toxicity study, administration of the compounds was performed orally to mice at single doses. The mice were observed for clinical signs, body weight effects and mortality for 14 days, after which they were sacrificed for gross organ necropsy. The body weight did not vary after administration, and the autoptic analysis failed to show appreciable macroscopic alterations of internal organs. Generally, the compounds exhibited low toxic effects as required for further in vivo therapeutic studies.

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Non-substituted N-heteroaromatic selenosemicarbazone metal complexes induce apoptosis in cancer cells via activation of mitochondrial pathway

Cited by 36 publications

References 60 publications

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

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

Gold(III) compounds-mediated inhibition of lung cancer cell proliferation

High antioxidative potential and low toxic effects of selenosemicarbazone metal complexes

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