Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl-d-aspartate (NMDA) Receptor Antagonist

Research output: Contribution to journalJournal articleResearchpeer-review

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Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl-d-aspartate (NMDA) Receptor Antagonist. / Gynther, Mikko; Proietti Silvestri, Ilaria; Hansen, Jacob C; Hansen, Kasper B; Malm, Tarja; Ishchenko, Yevheniia; Larsen, Younes; Han, Liwei; Kayser, Silke; Auriola, Seppo; Petsalo, Aleksanteri; Nielsen, Birgitte; Pickering, Darryl S; Bunch, Lennart.

In: Journal of Medicinal Chemistry, Vol. 60, No. 23, 14.12.2017, p. 9885-9904.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Gynther, M, Proietti Silvestri, I, Hansen, JC, Hansen, KB, Malm, T, Ishchenko, Y, Larsen, Y, Han, L, Kayser, S, Auriola, S, Petsalo, A, Nielsen, B, Pickering, DS & Bunch, L 2017, 'Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl-d-aspartate (NMDA) Receptor Antagonist' Journal of Medicinal Chemistry, vol. 60, no. 23, pp. 9885-9904. https://doi.org/10.1021/acs.jmedchem.7b01624

APA

Gynther, M., Proietti Silvestri, I., Hansen, J. C., Hansen, K. B., Malm, T., Ishchenko, Y., ... Bunch, L. (2017). Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl-d-aspartate (NMDA) Receptor Antagonist. Journal of Medicinal Chemistry, 60(23), 9885-9904. https://doi.org/10.1021/acs.jmedchem.7b01624

Vancouver

Gynther M, Proietti Silvestri I, Hansen JC, Hansen KB, Malm T, Ishchenko Y et al. Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl-d-aspartate (NMDA) Receptor Antagonist. Journal of Medicinal Chemistry. 2017 Dec 14;60(23):9885-9904. https://doi.org/10.1021/acs.jmedchem.7b01624

Author

Gynther, Mikko ; Proietti Silvestri, Ilaria ; Hansen, Jacob C ; Hansen, Kasper B ; Malm, Tarja ; Ishchenko, Yevheniia ; Larsen, Younes ; Han, Liwei ; Kayser, Silke ; Auriola, Seppo ; Petsalo, Aleksanteri ; Nielsen, Birgitte ; Pickering, Darryl S ; Bunch, Lennart. / Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl-d-aspartate (NMDA) Receptor Antagonist. In: Journal of Medicinal Chemistry. 2017 ; Vol. 60, No. 23. pp. 9885-9904.

Bibtex

@article{8a429ff26a8b43b6a98e6a023bde2da9,
title = "Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl-d-aspartate (NMDA) Receptor Antagonist",
abstract = "The most common solid tumors show intrinsic multidrug resistance (MDR) or inevitably acquire such when treated with anticancer drugs. In this work, we describe the discovery of a peripherally restricted, potent, competitive NMDA receptor antagonist 1l by a structure-activity study of the broad-acting ionotropic glutamate receptor antagonist 1a. Subsequently, we demonstrate that 1l augments the cytotoxic action of sorafenib in murine hepatocellular carcinoma cells. The underlying biological mechanism was shown to be interference with the lipid signaling pathway, leading to reduced expression of MDR transporters and thereby an increased accumulation of sorafenib in the cancer cells. Interference with lipid signaling pathways by NMDA receptor inhibition is a novel and promising strategy for reversing transporter-mediated chemoresistance in cancer cells.",
keywords = "Journal Article",
author = "Mikko Gynther and {Proietti Silvestri}, Ilaria and Hansen, {Jacob C} and Hansen, {Kasper B} and Tarja Malm and Yevheniia Ishchenko and Younes Larsen and Liwei Han and Silke Kayser and Seppo Auriola and Aleksanteri Petsalo and Birgitte Nielsen and Pickering, {Darryl S} and Lennart Bunch",
year = "2017",
month = "12",
day = "14",
doi = "10.1021/acs.jmedchem.7b01624",
language = "English",
volume = "60",
pages = "9885--9904",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "23",

}

RIS

TY - JOUR

T1 - Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl-d-aspartate (NMDA) Receptor Antagonist

AU - Gynther, Mikko

AU - Proietti Silvestri, Ilaria

AU - Hansen, Jacob C

AU - Hansen, Kasper B

AU - Malm, Tarja

AU - Ishchenko, Yevheniia

AU - Larsen, Younes

AU - Han, Liwei

AU - Kayser, Silke

AU - Auriola, Seppo

AU - Petsalo, Aleksanteri

AU - Nielsen, Birgitte

AU - Pickering, Darryl S

AU - Bunch, Lennart

PY - 2017/12/14

Y1 - 2017/12/14

N2 - The most common solid tumors show intrinsic multidrug resistance (MDR) or inevitably acquire such when treated with anticancer drugs. In this work, we describe the discovery of a peripherally restricted, potent, competitive NMDA receptor antagonist 1l by a structure-activity study of the broad-acting ionotropic glutamate receptor antagonist 1a. Subsequently, we demonstrate that 1l augments the cytotoxic action of sorafenib in murine hepatocellular carcinoma cells. The underlying biological mechanism was shown to be interference with the lipid signaling pathway, leading to reduced expression of MDR transporters and thereby an increased accumulation of sorafenib in the cancer cells. Interference with lipid signaling pathways by NMDA receptor inhibition is a novel and promising strategy for reversing transporter-mediated chemoresistance in cancer cells.

AB - The most common solid tumors show intrinsic multidrug resistance (MDR) or inevitably acquire such when treated with anticancer drugs. In this work, we describe the discovery of a peripherally restricted, potent, competitive NMDA receptor antagonist 1l by a structure-activity study of the broad-acting ionotropic glutamate receptor antagonist 1a. Subsequently, we demonstrate that 1l augments the cytotoxic action of sorafenib in murine hepatocellular carcinoma cells. The underlying biological mechanism was shown to be interference with the lipid signaling pathway, leading to reduced expression of MDR transporters and thereby an increased accumulation of sorafenib in the cancer cells. Interference with lipid signaling pathways by NMDA receptor inhibition is a novel and promising strategy for reversing transporter-mediated chemoresistance in cancer cells.

KW - Journal Article

U2 - 10.1021/acs.jmedchem.7b01624

DO - 10.1021/acs.jmedchem.7b01624

M3 - Journal article

VL - 60

SP - 9885

EP - 9904

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 23

ER -

ID: 186867038