Studies on the cytotoxic, apoptotic and antitumoral effects of Au(III) and Pt(II) complexes of 1, 10-phenanthroline on V79 379A and A549 cell lines

Bostancıoğlu, Rakibe Beklem; Işık, Kenan; Genç, Hatice; Benkli, Kadriye; Koparal, Ayşe Tansu

doi:10.3109/14756366.2011.596835

Cited by 21 publications

(13 citation statements)

References 33 publications

(64 reference statements)

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“…We demonstrated for the first time that this platinum complex (PT) inhibited the colony forming ability of human colorectal cancer cells in a dose dependent manner. A similar polyamine complex of Pt(II) inhibited colony formation in breast cancer cells [46] and Pt (II) complex of 1, 10-phenanthroline exhibited antitumor effect in lung cancer [47]. Inhibition of cell proliferation is mainly mediated by apoptosis that plays an important role in fighting cancer.…”

Section: Discussionmentioning

confidence: 99%

A novel coordination complex of platinum (PT) induces cell death in colorectal cancer by altering redox balance and modulating MAPK pathway

et al. 2020

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Background Colorectal cancer (CRC) is a heterogeneous tumor having various genetic alterations. The current treatment options had limited impact on disease free survival due to therapeutic resistance. Novel anticancer agents are needed to treat CRC specifically metastatic colorectal cancer. A novel coordination complex of platinum, (salicylaldiminato)Pt(II) complex with dimethylpropylene linkage (PT) exhibited potential anti-cancer activity. In this study, we explored the molecular mechanism of PT-induced cell death in colorectal cancer. Methods Colony formation was evaluated using the clonogenic assay. Apoptosis, cell cycle analysis, reactive oxygen species, mitochondrial membrane potential and caspase-3/− 7 were assessed by flow cytometry. Glutathione level was detected by colorimetric assay. PT-induced alteration in pro-apoptotic/ anti-apoptotic proteins and other signaling pathways were investigated using western blotting. P38 downregulation was performed using siRNA. Results In the present study, we explored the molecular mechanism of PT-mediated inhibition of cell proliferation in colorectal cancer cells. PT significantly inhibited the colony formation in human colorectal cancer cell lines (HT-29, SW480 and SW620) by inducing apoptosis and necrosis. This platinum complex was shown to significantly increase the reactive oxygen species (ROS) generation, depletion of glutathione and reduced mitochondrial membrane potential in colorectal cancer cells. Exposure to PT resulted in the downregulation of anti-apoptotic proteins (Bcl2, BclxL, XIAP) and alteration in Cyclins expression. Furthermore, PT increased cytochrome c release into cytosol and enhanced PARP cleavage leading to activation of intrinsic apoptotic pathway. Moreover, pre-treatment with ROS scavenger N-acetylcysteine (NAC) attenuated apoptosis suggesting that PT-induced apoptosis was driven by oxidative stress. Additionally, we show that PT-induced apoptosis was mediated by activating p38 MAPK and inhibiting AKT pathways. This was demonstrated by using chemical inhibitor and siRNA against p38 kinase which blocked the cytochrome c release and apoptosis in colorectal cancer cells. Conclusion Collectively, our data demonstrates that the platinum complex (PT) exerts its anti-proliferative effect on CRC by ROS-mediated apoptosis and activating p38 MAPK pathway. Thus, our findings reveal a novel mechanism of action for PT on colorectal cancer cells and may have therapeutic implication.

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Section: Discussionmentioning

confidence: 99%

A novel coordination complex of platinum (PT) induces cell death in colorectal cancer by altering redox balance and modulating MAPK pathway

et al. 2020

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“…We previously reported our investigation on Au(III) and Pt(II) complexes of 1,10-phenanthroline (phen), namely, [21,23]. Here, the investigation was extended to a new series of gold(III) complexes.…”

Section: Discussionmentioning

confidence: 94%

“…After 24 h of seeding, cells were treated with various doses of [Au (L)B](PF 6 ) 2 , [(Au(L)B)Pt]Cl 2 , and cisplatin for 12 h. The assay was performed as described previously [21]. Fluorescent images were viewed using an Olympus fluorescence microscope (Olympus IX70; Olympus, Tokyo, Japan).…”

Section: Dapi Stainingmentioning

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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“…The principles behind the development of chrysotherapeutic agents can be used to synthesize gold complexes that contain various functional ligands with distinctive pharmacological, chemical, physical, and biological properties (Bostancioglu et al, 2012, Al-Jaroudi et al, 2014). In vitro and in vivo studies have revealed that gold(I) and gold(III) complexes significantly impede cancer cell growth and hence can be used as an alternative to platinum-based anticancer drugs (Lima and Rodriguez, 2011, Che and Sun, 2011).…”

Section: Introductionmentioning

confidence: 99%

Gold-containing compound BDG-I inhibits the growth of A549 lung cancer cells through the deregulation of miRNA expression

Alhoshani

Alrashdi

Alhosaini

et al. 2018

Saudi Pharmaceutical Journal

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Gold complex bis(diethyldithiocarbamato-gold(I)) bis(diphenylphosphino) methane (BDG-I) is cytotoxic toward different cancer cell lines. We compared the cytotoxic effect of BDG-I with that of cisplatin in the A549 lung cancer cell line. Additionally, we investigated the molecular mechanism underlying the toxic effect of BDG-I toward the A549 cell line and the identification of cancer-related miRNAs likely to be involved in killing the lung cancer cells. Further, X-ray crystallographic data of the compound were acquired. Using microarray, global miRNA expression profiling in BDG-I-treated A549 cells revealed 64 upregulated and 86 downregulated miRNAs, which targeted 4689 and 2498 genes, respectively. Biological network connectivity of the miRNAs was significantly higher for the upregulated miRNAs than for the downregulated miRNAs. Two of the 10 most upregulated miRNAs (hsa-mir-20a-5p and hsa-mir-15b-5p) were associated with lung cancer. AmiGo2 server and Panther pathway analyses indicated significant enrichment in transcription regulation of miRNA target genes that promote intrinsic kinase-mediated signaling, TGF-β, and GnRH signaling pathways, as well as oxidative stress responses. BDG-I crystal structure X-ray diffraction studies revealed gold–gold intramolecular interaction [Au…Au = 3.1198 (3) Å] for a single independent molecule, reported to be responsible for its activity against cancer. Our present study sheds light on the development of novel gold complex with favorable anti-cancer therapeutic functionality.

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Studies on the cytotoxic, apoptotic and antitumoral effects of Au(III) and Pt(II) complexes of 1, 10-phenanthroline on V79 379A and A549 cell lines

Cited by 21 publications

References 33 publications

A novel coordination complex of platinum (PT) induces cell death in colorectal cancer by altering redox balance and modulating MAPK pathway

A novel coordination complex of platinum (PT) induces cell death in colorectal cancer by altering redox balance and modulating MAPK pathway

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

Gold-containing compound BDG-I inhibits the growth of A549 lung cancer cells through the deregulation of miRNA expression

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