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Effect of flupirtine on the growth and viability of U373 malignant glioma cells.

Panchanathan E, Ramanathan G, Lakkakula BV - Cancer Biol Med (2013)

Bottom Line: Furthermore, flupirtine antagonizes glutamate- and NMDA-induced intracellular levels of Ca(2+) and counteracts the effects of focal cerebral ischemia.Variations in the growth of U373 MG cells in 5 mM N-methyl-D-aspartate (NMDA), 1 mM flupirtine, and combined treatment indicated the antagonistic effects of NMDA and flupirtine on MG cell lines.Flupirtine has neuroprotective effect of on U373 MG cells, which limits its use in the pain management of brain tumors.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Sri Ramachandra University, Chennai 600118, India.

ABSTRACT

Objective: Flupirtine is a non-opioid analgesic without antipyretic or antiphlogistic properties but with favorable tolerability in humans. This analgesic also exhibits neuroprotective activities. Furthermore, flupirtine antagonizes glutamate- and NMDA-induced intracellular levels of Ca(2+) and counteracts the effects of focal cerebral ischemia. Although flupirtine has been used to relieve pain caused by different diseases and clinical procedures, information on the safety and efficacy of flupirtine is limited. The present study was conducted to investigate the neuroprotective effects of flupirtine on U373 malignant glioma (MG) cell lines.

Methods: Cell viability and cell cycle analysis was performed by MTT assay and flow cytometry, respectively.

Results: Variations in the growth of U373 MG cells in 5 mM N-methyl-D-aspartate (NMDA), 1 mM flupirtine, and combined treatment indicated the antagonistic effects of NMDA and flupirtine on MG cell lines. The variation in the percentage of gated cell population in different cell cycle phases showed significant variations after 48 h of treatment.

Conclusion: Flupirtine has neuroprotective effect of on U373 MG cells, which limits its use in the pain management of brain tumors. This property warrants further studies using animal models and large-scale clinical trials.

No MeSH data available.


Related in: MedlinePlus

Distribution of gated cell population in different cell cycle phases after treatment with flupirtine, NMDA, and their combination (A. 24 h; B. 48 h).
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f3: Distribution of gated cell population in different cell cycle phases after treatment with flupirtine, NMDA, and their combination (A. 24 h; B. 48 h).

Mentions: Figure 2 shows the gated U373 MG cell population in response to flupirtine, NMDA, and combined treatment. Figure 3 illustrates the effect of flupirtine, NMDA, and combined treatment on the cell cycle phases of U373 MG cells for 24 and 48 h of incubation. In particular, the cells treated with 5 mM NMDA for 24 h showed a higher percentage of G0-G1 cell cycle phase than the control cells (Figure 3). The flupirtine-treated cells showed lower G0-G1 cell cycle phase at 1 mM than the control cells. The percentage of gated cell population in different cell cycle phases varied after 24 and 48 h of treatment (Table 1). Levene’s test and F-test results showed that the significant variations in cell cycle phases were found only after 48 h but not after 24 h of treatment. The combined NMDA and flupirtine treatment decreased the percentage of cells at G0-G1 cell cycle phase compared with NMDA alone. The cells treated for 48 h showed the same antagonistic effects of NMDA and flupirtine drugs compared with the control cells and those treated at 24 h. The percentage of cells in G0-G1 cell cycle phase increased in NMDA-treated cells but decreased in flupirtine-treated cells. The combined treatment reduced the percentage of cells in G0-G1 cell cycle phase but increased the percentage of cells of other cell cycle phases (Figure 3).


Effect of flupirtine on the growth and viability of U373 malignant glioma cells.

Panchanathan E, Ramanathan G, Lakkakula BV - Cancer Biol Med (2013)

Distribution of gated cell population in different cell cycle phases after treatment with flupirtine, NMDA, and their combination (A. 24 h; B. 48 h).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860341&req=5

f3: Distribution of gated cell population in different cell cycle phases after treatment with flupirtine, NMDA, and their combination (A. 24 h; B. 48 h).
Mentions: Figure 2 shows the gated U373 MG cell population in response to flupirtine, NMDA, and combined treatment. Figure 3 illustrates the effect of flupirtine, NMDA, and combined treatment on the cell cycle phases of U373 MG cells for 24 and 48 h of incubation. In particular, the cells treated with 5 mM NMDA for 24 h showed a higher percentage of G0-G1 cell cycle phase than the control cells (Figure 3). The flupirtine-treated cells showed lower G0-G1 cell cycle phase at 1 mM than the control cells. The percentage of gated cell population in different cell cycle phases varied after 24 and 48 h of treatment (Table 1). Levene’s test and F-test results showed that the significant variations in cell cycle phases were found only after 48 h but not after 24 h of treatment. The combined NMDA and flupirtine treatment decreased the percentage of cells at G0-G1 cell cycle phase compared with NMDA alone. The cells treated for 48 h showed the same antagonistic effects of NMDA and flupirtine drugs compared with the control cells and those treated at 24 h. The percentage of cells in G0-G1 cell cycle phase increased in NMDA-treated cells but decreased in flupirtine-treated cells. The combined treatment reduced the percentage of cells in G0-G1 cell cycle phase but increased the percentage of cells of other cell cycle phases (Figure 3).

Bottom Line: Furthermore, flupirtine antagonizes glutamate- and NMDA-induced intracellular levels of Ca(2+) and counteracts the effects of focal cerebral ischemia.Variations in the growth of U373 MG cells in 5 mM N-methyl-D-aspartate (NMDA), 1 mM flupirtine, and combined treatment indicated the antagonistic effects of NMDA and flupirtine on MG cell lines.Flupirtine has neuroprotective effect of on U373 MG cells, which limits its use in the pain management of brain tumors.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Sri Ramachandra University, Chennai 600118, India.

ABSTRACT

Objective: Flupirtine is a non-opioid analgesic without antipyretic or antiphlogistic properties but with favorable tolerability in humans. This analgesic also exhibits neuroprotective activities. Furthermore, flupirtine antagonizes glutamate- and NMDA-induced intracellular levels of Ca(2+) and counteracts the effects of focal cerebral ischemia. Although flupirtine has been used to relieve pain caused by different diseases and clinical procedures, information on the safety and efficacy of flupirtine is limited. The present study was conducted to investigate the neuroprotective effects of flupirtine on U373 malignant glioma (MG) cell lines.

Methods: Cell viability and cell cycle analysis was performed by MTT assay and flow cytometry, respectively.

Results: Variations in the growth of U373 MG cells in 5 mM N-methyl-D-aspartate (NMDA), 1 mM flupirtine, and combined treatment indicated the antagonistic effects of NMDA and flupirtine on MG cell lines. The variation in the percentage of gated cell population in different cell cycle phases showed significant variations after 48 h of treatment.

Conclusion: Flupirtine has neuroprotective effect of on U373 MG cells, which limits its use in the pain management of brain tumors. This property warrants further studies using animal models and large-scale clinical trials.

No MeSH data available.


Related in: MedlinePlus