Graphene functionalized with arginine decreases the development of glioblastoma multiforme tumor in a gene-dependent manner

Ewa Sawosz; Slawomir Jaworski; Marta Kutwin; Krishna Prasad Vadalasetty; Marta Grodzik; Mateusz Wierzbicki; Natalia Kurantowicz; Barbara Strojny; Anna Hotowy; Ludwika Lipińska; Joanna Jagiełło; André Chwalibog

doi:10.3390/ijms161025214

Graphene functionalized with arginine decreases the development of glioblastoma multiforme tumor in a gene-dependent manner

Ewa Sawosz, Slawomir Jaworski, Marta Kutwin, Krishna Prasad Vadalasetty, Marta Grodzik, Mateusz Wierzbicki, Natalia Kurantowicz, Barbara Strojny, Anna Hotowy, Ludwika Lipińska, Joanna Jagiełło, André Chwalibog

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Abstract

Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM) cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the activity of graphene. Experiments were performed in vitro with GBM U87 cells and in vivo with GBM tumors cultured on chicken embryo chorioallantoic membranes. The measurements included cell morphology, mortality, viability, tumor morphology, histology, and gene expression. The cells and tumors were treated with reduced graphene oxide (rGO) and rGO functionalized with arginine (rGO + Arg) or proline (rGO + Pro). The results confirmed the anticancer effect of graphene on GBM cells and tumor tissue. After functionalization with amino acids, nanoparticles were distributed more specifically, and the flakes of graphene were less agglomerated. The molecule of rGO + Arg did not increase the expression of TP53 in comparison to rGO, but did not increase the expression of MDM2 or the MDM2/TP53 ratio in the tumor, suggesting that arginine may block MDM2 expression. The expression of NQO1, known to be a strong protector of p53 protein in tumor tissue, was greatly increased. The results indicate that the complex of rGO + Arg has potential in GBM therapy.

Original language	English
Journal	International Journal of Molecular Sciences (Online)
Volume	16
Issue number	10
Pages (from-to)	25214-25233
Number of pages	20
ISSN	1661-6596
DOIs	https://doi.org/10.3390/ijms161025214
Publication status	Published - 23 Oct 2015

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Sawosz, E., Jaworski, S., Kutwin, M., Vadalasetty, K. P., Grodzik, M., Wierzbicki, M., Kurantowicz, N., Strojny, B., Hotowy, A., Lipińska, L., Jagiełło, J., & Chwalibog, A. (2015). Graphene functionalized with arginine decreases the development of glioblastoma multiforme tumor in a gene-dependent manner. International Journal of Molecular Sciences (Online), 16(10), 25214-25233. https://doi.org/10.3390/ijms161025214

Graphene functionalized with arginine decreases the development of glioblastoma multiforme tumor in a gene-dependent manner. / Sawosz, Ewa; Jaworski, Slawomir; Kutwin, Marta et al.

In: International Journal of Molecular Sciences (Online), Vol. 16, No. 10, 23.10.2015, p. 25214-25233.

Research output: Contribution to journal › Journal article › Research › peer-review

Sawosz, E, Jaworski, S, Kutwin, M, Vadalasetty, KP, Grodzik, M, Wierzbicki, M, Kurantowicz, N, Strojny, B, Hotowy, A, Lipińska, L, Jagiełło, J & Chwalibog, A 2015, 'Graphene functionalized with arginine decreases the development of glioblastoma multiforme tumor in a gene-dependent manner', International Journal of Molecular Sciences (Online), vol. 16, no. 10, pp. 25214-25233. https://doi.org/10.3390/ijms161025214

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abstract = "Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM) cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the activity of graphene. Experiments were performed in vitro with GBM U87 cells and in vivo with GBM tumors cultured on chicken embryo chorioallantoic membranes. The measurements included cell morphology, mortality, viability, tumor morphology, histology, and gene expression. The cells and tumors were treated with reduced graphene oxide (rGO) and rGO functionalized with arginine (rGO + Arg) or proline (rGO + Pro). The results confirmed the anticancer effect of graphene on GBM cells and tumor tissue. After functionalization with amino acids, nanoparticles were distributed more specifically, and the flakes of graphene were less agglomerated. The molecule of rGO + Arg did not increase the expression of TP53 in comparison to rGO, but did not increase the expression of MDM2 or the MDM2/TP53 ratio in the tumor, suggesting that arginine may block MDM2 expression. The expression of NQO1, known to be a strong protector of p53 protein in tumor tissue, was greatly increased. The results indicate that the complex of rGO + Arg has potential in GBM therapy.",

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AU - Vadalasetty, Krishna Prasad

AU - Grodzik, Marta

AU - Wierzbicki, Mateusz

AU - Kurantowicz, Natalia

AU - Strojny, Barbara

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AU - Lipińska, Ludwika

AU - Jagiełło, Joanna

AU - Chwalibog, André

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N2 - Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM) cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the activity of graphene. Experiments were performed in vitro with GBM U87 cells and in vivo with GBM tumors cultured on chicken embryo chorioallantoic membranes. The measurements included cell morphology, mortality, viability, tumor morphology, histology, and gene expression. The cells and tumors were treated with reduced graphene oxide (rGO) and rGO functionalized with arginine (rGO + Arg) or proline (rGO + Pro). The results confirmed the anticancer effect of graphene on GBM cells and tumor tissue. After functionalization with amino acids, nanoparticles were distributed more specifically, and the flakes of graphene were less agglomerated. The molecule of rGO + Arg did not increase the expression of TP53 in comparison to rGO, but did not increase the expression of MDM2 or the MDM2/TP53 ratio in the tumor, suggesting that arginine may block MDM2 expression. The expression of NQO1, known to be a strong protector of p53 protein in tumor tissue, was greatly increased. The results indicate that the complex of rGO + Arg has potential in GBM therapy.

AB - Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM) cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the activity of graphene. Experiments were performed in vitro with GBM U87 cells and in vivo with GBM tumors cultured on chicken embryo chorioallantoic membranes. The measurements included cell morphology, mortality, viability, tumor morphology, histology, and gene expression. The cells and tumors were treated with reduced graphene oxide (rGO) and rGO functionalized with arginine (rGO + Arg) or proline (rGO + Pro). The results confirmed the anticancer effect of graphene on GBM cells and tumor tissue. After functionalization with amino acids, nanoparticles were distributed more specifically, and the flakes of graphene were less agglomerated. The molecule of rGO + Arg did not increase the expression of TP53 in comparison to rGO, but did not increase the expression of MDM2 or the MDM2/TP53 ratio in the tumor, suggesting that arginine may block MDM2 expression. The expression of NQO1, known to be a strong protector of p53 protein in tumor tissue, was greatly increased. The results indicate that the complex of rGO + Arg has potential in GBM therapy.

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Graphene functionalized with arginine decreases the development of glioblastoma multiforme tumor in a gene-dependent manner

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