Comparative study of the cytotoxic effect of microcistin-LR and purified extracts from Microcystis aeruginosa on a kidney cell line

Dias, Elsa; Andrade, M. I. Paz; Alverca, Elsa; Pereira, Paulo; Batoréu, M.C.; Jordan, Peter; Silva, Maria João

doi:10.1016/j.toxicon.2009.01.029

Cited by 46 publications

(26 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our studies with Vero-E6 cell line we have consistently observed that MCLR induces a concentration-dependent decrease of cell viability [26,27,29,30]. This was achieved using distinct cell viability assays (MTT, Neutral Red and LDH release) and distinct toxin sources (commercially available MCLR and M. aeruginosa extracts).…”

Section: Cell Viabilitymentioning

confidence: 89%

“…This was achieved using distinct cell viability assays (MTT, Neutral Red and LDH release) and distinct toxin sources (commercially available MCLR and M. aeruginosa extracts). We observed that the most sensitive methods for cytotoxicity evaluation were MTT and Neutral Red assays [26,27,29] and that the response of pure toxin and cyanobacterial extracts was quite similar with cytotoxic thresholds within 22-50 µM of MCLR ( Table 1). The MCLR-induced loss of Vero-E6 viability was attributed to apoptosis and necrosis [29,30] as widely described for various cell types in vitro and in vivo [18,31,32].…”

Section: Cell Viabilitymentioning

confidence: 96%

“…Surprisingly, we observed that the dose-response curve of cell viability decrease induced by MCLR was quite similar in Vero-E6 and in liver-derived cell lines [26]. Since then, we have been demonstrated that MCLR induces a multiplicity of effects on Vero cells within a wide range of concentrations [26][27][28][29][30], according to a dose-effect relationship ( Figure 3). …”

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

The Kidney Vero-E6 Cell Line: A Suitable Model to Study the Toxicity of Microcystins

Menezes¹,

Valério²,

Dias³

2013

New Insights Into Toxicity and Drug Testing

Self Cite

View full text Add to dashboard Cite

Section: Cell Viabilitymentioning

confidence: 89%

Section: Cell Viabilitymentioning

confidence: 96%

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

The Kidney Vero-E6 Cell Line: A Suitable Model to Study the Toxicity of Microcystins

Menezes¹,

Valério²,

Dias³

2013

New Insights Into Toxicity and Drug Testing

Self Cite

View full text Add to dashboard Cite

“…In previous studies we demonstrated that MCLR induces cytotoxic effects (organelle changes/damages, cell lysis, apoptosis and necrosis) on the kidney-derived Vero-E6 cell line Dias et al, 2009). These effects were observed above 5 lM, according to a dose and time-dependent manner.…”

Section: Introductionmentioning

confidence: 92%

Microcystin-LR activates the ERK1/2 kinases and stimulates the proliferation of the monkey kidney-derived cell line Vero-E6

Dias

Matos

Pereira

et al. 2010

Toxicology in Vitro

Self Cite

View full text Add to dashboard Cite

a b s t r a c tMicrocystin-LR (MCLR) is a peptide produced by freshwater cyanobacteria that induces severe hepatotoxicity in humans and animals. MCLR is also a potent tumour promoter and it has been proposed that this activity is mediated by the inhibition of protein phosphatases PP1/PP2A, possibly through the activation of proto-oncogenes c-jun, c-fos and c-myc. However, the mechanisms underlying MCLR-induced tumour promotion are still largely unknown, particularly in non-liver cells. In previous studies we have demonstrated that micromolar concentrations of MCLR induce cytotoxic effects in the kidney Vero-E6 cell line. The purpose of the present work was to evaluate whether the exposure to subcytotoxic concentrations of MCLR was sufficient to induce the proliferation of Vero-E6 cells. Through BrdU incorporation assay we show that at nanomolar concentrations MCLR stimulates cell cycle progression in Vero-E6 kidney cell line. Moreover, the analysis of mitogen-activated protein kinases p38, JNK and ERK1/2 activity revealed that the proliferative effect of MCLR is associated with the activation of the pro-proliferative ERK1/2 pathway. These results emphasise the importance to confirm in vivo the impact of MCLR on tumour promotion at kidney level.

show abstract

“…When the IC 50 values of MC-LR in the two cell lines were compared, HEK-293 had lower values than the ACHN cells at 24 h post-incubation in both MTT and SRB assays, suggesting that MC-LR is more cytotoxic to normal embryonic kidney cells than to kidney adenocarcinoma cells. Dias et al (2009) significant reduction of cell viability when the same cell line was exposed to 30 mM MC-LR for the same incubation period. Other literature has reported a significant reduction in the viability of rat Sertoli cells upon exposure to MC-LR at 50 and 500 nM for 24 h and at 10.05-20.10 mM (10-20 mg ml…”

Section: Discussionmentioning

confidence: 91%

Microcystin-LR-induced cytotoxicity and apoptosis in human embryonic kidney and human kidney adenocarcinoma cell lines

et al. 2015

View full text Add to dashboard Cite

Microcystin-LR (MC-LR) is a potent hepatotoxin, and increasing evidence suggests that it might also induce kidney injury. The aim of the present work was to evaluate the cytotoxicity and possible apoptotic effects of MC-LR on a human embryonic kidney cell line (HEK-293) and human kidney adenocarcinoma cell line (ACHN). Cells were exposed for 24 h to pure MC-LR (1.0-200 mM) and the cytotoxic effects were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulphorhodamine B (SRB) cell viability assays. Cell viability in both cell lines was significantly decreased after treatment with MC-LR at 50 mM for 24 h (P,0.001). Moreover, MC-LR-treated ACHN and HEK-293 cells exhibited a marked dosedependent loss of confluence as judged by phase-contrast microscopy. Similarly, fluorescence microscopic observations following acridine orange-ethidium bromide (AO/EB) staining confirmed that both cell types were undergoing apoptosis after treatment with MC-LR for 24 h. Expression of three apoptosis-related genes, Bax, Survivin and p53, was analysed by quantitative reverse transcriptase PCR analysis. Both Bax and p53 functioned as promoters of MC-LRmediated apoptosis in ACHN and HEK-293 cells. The Survivin gene acted as a suppressor of apoptosis at lower MC-LR concentration (1 mM) and the gene was upregulated at higher MC-LR concentration (10 mM) (P,0.001). Significant increases of caspase 3 (P,0.0001) and caspase 9 (P,0.0001) activity were detected in both cell lines after exposure to MC-LR for 24 h, indicating the MC-LR induces cytotoxicity and a marked apoptosis in both ACHN and HEK-293 kidney cell lines.

show abstract

Comparative study of the cytotoxic effect of microcistin-LR and purified extracts from Microcystis aeruginosa on a kidney cell line

Cited by 46 publications

References 30 publications

The Kidney Vero-E6 Cell Line: A Suitable Model to Study the Toxicity of Microcystins

The Kidney Vero-E6 Cell Line: A Suitable Model to Study the Toxicity of Microcystins

Microcystin-LR activates the ERK1/2 kinases and stimulates the proliferation of the monkey kidney-derived cell line Vero-E6

Microcystin-LR-induced cytotoxicity and apoptosis in human embryonic kidney and human kidney adenocarcinoma cell lines

Contact Info

Product

Resources

About