Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity

Genç, Gürkan; Kilinc, Veli; Bedir, Abdülkerim; Özkaya, Ozan

doi:10.3109/0886022x.2014.926755

Cited by 8 publications

(4 citation statements)

References 46 publications

(48 reference statements)

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“…Our previous study reported that IC 50 of imatinib in SQUU-A cells calculated by RTCA system and WST-8 assay were 4 µM and 60 µM, respectively (sensitivity of 15 times) (6,7). Other research groups reported that IC 50 of cisplatin in HK-2 cells calculated by RTCA system and WST-8 assay were 0.76 µM and 25 µM, respectively (sensitivity of 33 times) (30,31). These previous data supported our data to show validity.…”

Section: Discussionsupporting

confidence: 91%

Evaluation of IC50 levels immediately after treatment with anticancer reagents using a real‑time cell monitoring device

et al. 2019

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A real-time cell-monitoring analysis (RTCA) system was previously developed based on the change in impedance when cells attach and spread in a culture dish coated with a gold microelectrode array. However, the potential applications of this system have not yet been fully demonstrated. The purpose of this study was to test the utility of the RTCA system to determine the cytotoxicity of four anticancer agents in carcinoma cells. The results were compared with those of the conventional WST-8 assay at the endpoint to determine the potential of the RTCA system as a new real-time assay method to evaluate cytotoxicity. iCELLigence was used as the RTCA system in this study. Suspensions of oral squamous cell carcinoma (OSCC) cell lines were seeded (2x10 4 cells/well) onto the E-plate (the culture plate of the iCELLigence system). After 24 h of culture, anticancer agents were added to each well, and changes in electrical impedance (cell index, CI) were recorded for another 72 h of culture. Cell proliferation was detected in real-time by the RTCA device in an automated, high throughput manner. Then, the IC 50 profiles of the four anticancer agents were calculated based on the real-time cell index values. The results indicated that the RTCA system was useful in evaluating cytotoxic reactions immediately after the addition of the anticancer agents as it was able to record the data in real-time. Furthermore, the IC 50 levels measured by the real-time assay were lower than those measured by the endpoint assay. Thus, RTCA systems can be used to evaluate chemotherapeutic agents in cancer cells as well as their side effects in normal cells.

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Section: Discussionsupporting

confidence: 91%

Evaluation of IC50 levels immediately after treatment with anticancer reagents using a real‑time cell monitoring device

et al. 2019

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“…Pioglitazone, along its ability of suppress oxidative stress and damage through improving antioxidant capacity, has been reported to have a role in suppression of MAPK, Nf-kB signaling pathways and inhibition of TNFα with an IC 50 dose of 1.61 M at 24th hour and 2.85 M at 48th hour [14,15]. In order to evaluate the anti-proliferative effect of pioglitazone as single agents, we used several human non small lung cancer (NSCLC) cell lines: A549, H1299, H460, H1975, HCC827 and human bronchial epithelial cells, Beas2B, as control.…”

Section: Effect Of Pioglitazone On Proliferation Migration and Apoptmentioning

confidence: 99%

Activity and molecular targets of pioglitazone via blockade of proliferation, invasiveness and bioenergetics in human NSCLC

Ciaramella

Sasso

Liello

et al. 2019

J Exp Clin Cancer Res

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Background: Pioglitazone, a synthetic peroxisome proliferator activated receptor (PPAR-γ) ligand, is known as an antidiabetic drug included in the thiazolidinediones (TZDs) class. It regulates the lipid and glucose cell metabolism and recently a role in the inhibition of numerous cancer cell processes has been described. Methods: In our work we investigate the anti-tumor effects of pioglitazone in in vitro models of non small cell lung cancer (NSCLC) and also, we generated ex-vivo three-dimensional (3D) cultures from human lung adenocarcinoma (ADK) as a model to test drug efficacy observed in vitro. The inhibitory effect of pioglitazone on cell proliferation, apoptosis and cell invasion in a panel of human NSCLC cell lines was evaluated by multiple assays. Results: Pioglitazone reduced proliferative and invasive abilities with an IC 50 ranging between 5 and 10 μM and induced apoptosis of NSCLC cells. mRNA microarray expression profiling showed a down regulation of MAPK, Myc and Ras genes after treatment with pioglitazone; altered gene expression was confirmed by protein analysis in a dose-related reduction of survivin and phosphorylated proteins levels of MAPK pathway. Interestingly mRNA microarray analysis showed also that pioglitazone affects TGFβ pathway, which is important in the epithelial-tomesenchimal transition (EMT) process, by down-regulating TGFβR1 and SMAD3 mRNA expression. In addition, extracellular acidification rate (ECAR) and a proportional reduction of markers of altered glucose metabolism in treated cells demonstrated also cell bioenergetics modulation by pioglitazone. Conclusions: Data indicate that PPAR-γ agonists represent an attractive treatment tool and by suppression of cell growth (in vitro and ex vivo models) and of invasion via blockade of MAPK cascade and TGFβ/SMADs signaling, respectively, and its role in cancer bioenergetics and metabolism indicate that PPAR-γ agonists represent an attractive treatment tool for NSCLC.

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“…Based on these outcomes, HK-2 cells have been used for nephrotoxicity in vitro testing of a variety of compounds, i.e. heavy metals (Bao et al 2013, Fujiki et al 2014), endotoxin (Quoilin et al 2012, Wang et al 2015, commonly used toxic chemicals like cisplatin, polymyxin and cyclosporine A (Genc et al 2014, Keirstead et al 2014, Vizza et al 2013 and also for characterization of oxidative stress after H 2 O 2 treatment (Lee et al 2013, Lin et al 2014. These experiments showed that HK-2 cells are substantially rather sensitive to oxidative damage and that is why this cell line has been predominantly accepted as a suitable in vitro model for studying nephrotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Acetaminophen Toxicity in Human Kidney HK-2 Cells

Vrbová

Roušarová²,

Brůčková³

et al. 2016

Physiol Res

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Acetaminophen (APAP) overdose causes liver injury, but in some cases it is associated also with renal impairment. While several studies exist in relation to acetaminophen nephrotoxicity, no reports have been published describing intracellular changes related to APAP nephrotoxicity in vitro. Because proximal tubular cells are considered to constitute a secondary site of drug-induced injury after hepatocytes, our study's aim was to estimate the toxicity in the human HK-2 cell line. We used a range of APAP concentrations (1-10 mM) to examine toxicity in the cells (1-48 h). We evaluated cell viability using the WST-1 and LDH tests. Cells impairment was also determined by monitoring ROS production, glutathione levels. We proved that HK-2 cells are able to metabolize acetaminophen. We observed moderate impairment of cells already after 1 h of treatment based on a finding of increased ROS production and decreased cell viability. After 24 h, the results showed significant cellular impairment at all tested concentrations except for 1 mM APAP, but no glutathione depletion was found. We conclude that HK-2 cells are susceptible to acetaminophen toxicity but, unlike hepatocytes, it might be not linked to glutathione depletion.

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Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity

Cited by 8 publications

References 46 publications

Evaluation of IC50 levels immediately after treatment with anticancer reagents using a real‑time cell monitoring device

Evaluation of IC50 levels immediately after treatment with anticancer reagents using a real‑time cell monitoring device

Activity and molecular targets of pioglitazone via blockade of proliferation, invasiveness and bioenergetics in human NSCLC

Characterization of Acetaminophen Toxicity in Human Kidney HK-2 Cells

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