In vitro Assessment of the Cytotoxicity of Gallium(III) Complexes with Isoniazid-Derived Hydrazones: Effects on Clonogenic Survival of HCT-116 Cells

Publication date: Available online 16 August 2019Source: Inorganica Chimica ActaAuthor(s): Gisele dos S.S. Firmino, Stephanie C. André, Zandora Hastenreiter, Vanessa Karen Campos, Mostafa A.L. Abdel-Salam, Elaine M. de Souza-Fagundes, Josane A. LessaAbstractCancer cells have high iron demand to mediate their rapid proliferation. Aiming to obtain cytotoxic compounds with potential iron metabolism disturbance in malignant cells, [Ga(HAPIH)(APIH)](NO3)2⋅2H2O (1) and [Ga(HPAmIH)(PAmIH)](NO3)2⋅2H2O (2) were synthesized with the iron chelators 2-acetylpyridine- and 2-pyridineformamide isonicotinoyl hydrazone (HAPIH and HPAmIH, respectively) and gallium(III), an iron(III) mimetic. The hydrazones and their gallium(III) complexes were assayed for their action against HL−60 (leukemia), MCF−7 (breast cancer), HCT−116 (colorectal carcinoma) and PC3 (prostate cancer) tumor cell lines, as well as non-malignant Human Embryonic Kidney 293 (HEK−293) cells. HAPIH and its complex 1 were the most cytotoxic compounds, with HCT−116 being the most susceptible line (IC50 = 1.6 μM for HAPIH and 0.4 μM for complex 1). Moreover, the compounds proved to be at least 25-fold less toxic to HEK−293 than to the tumor cells. According to clonogenic survival assays, the relative number of colonies formed by HCT−116 cells was reduced by around 95% after pretreatment with HAPIH and 1 at their IC90 concentrations (18 μM and 4 μM, respecti...
Source: Inorganica Chimica Acta - Category: Chemistry Source Type: research

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Studies have identified that the polymorphism rs10069690 of telomerase reverse transcriptase (TERT) is associated with cancer risk, but the results remain inconclusive. We performed a meta ‐analysis of 45 published studies including 329,035 cases and 730,940 controls. This meta‐analysis suggested that the TERT rs10069690 polymorphism may be a risk factor for cancer, especially breast cancer, ovarian cancer, and lung cancer. Further functional studies are warranted to reveal the ro le of the polymorphism in carcinogenesis. AbstractBackgroundStudies have identified that the telomerase reverse transcriptase (TERT) gene po...
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research
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Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: We found a highly reliable FI network, which revealed LIFR, PIK3R1, and MMP12 as novel prognostic biomarker candidates for GBC. These findings could accelerate biomarker discovery and therapeutic development in this cancer. Introduction Gallbladder cancer (GBC), the sixth most common gastrointestinal cancer, is an uncommon but challenging disease. Its incidence has recently increased highly worldwide (1). The risk factors for GBC include sex, aging, obesity, chronic cholecystitis, and cholelithiasis (2, 3). Because of the lack of an effective early diagnostic method, the disease often is not diagnosed ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions Several model systems are now available to characterize the MSC-tumour interplay in the TME. These offer early promise in establishing robust preclinical platforms for the identification of crucial molecular pathways and for the assessment of clinical efficacy of novel drugs to inhibit cancer development and progression. However, selection of the right model for a given study should be shaped on the purpose, and should also consider fixed biological, biochemical, and biophysical parameters according to the specific tumour type. Finally, in order to get reliable and useful results to be translated to the clinic...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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