Medium throughput biochemical compound screening identifies novel agents for pharmacotherapy of neurofibromatosis type 1

Galina Semenova; Dina S. Stepanova; Sergey M. Deyev; Jonathan Chernoff

doi:10.1016/j.biochi.2017.01.001

Medium throughput biochemical compound screening identifies novel agents for pharmacotherapy of neurofibromatosis type 1

Galina Semenova, Dina S. Stepanova, Sergey M. Deyev, Jonathan Chernoff

Cancer Signaling and Microenvironment (CSM)

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

The variable manifestation of phenotypes that occur in patients with neurofibromatosis type 1 (NF1) includes benign and malignant neurocutaneous tumors for which no adequate treatment exists. Cell-based screening of known bioactive compounds library identified the protein phosphatase 2A (PP2A) inhibitor Cantharidin and the L-type calcium channel blocker Nifedipine as potential candidates for NF1 pharmacotherapy. Validation of screening results using human NF1-associated malignant peripheral nerve sheath tumor (MPNST) cells showed that Cantharidin effectively impeded MPNST cell growth, while Nifedipine treatment significantly decreased local tumor growth in an MPNST xenograft animal model. These data suggest that inhibitors of PP2A, as well as calcium channel blockers, might be used in broader MPNST preclinical studies as single agents or in combinatorial therapeutic strategies.

Original language	English
Pages (from-to)	1-5
Number of pages	5
Journal	Biochimie
Volume	135
DOIs	https://doi.org/10.1016/j.biochi.2017.01.001
State	Published - Apr 1 2017

Keywords

Cantharidin
Chemical screening
Neurofibromatosis type 1
Nifedipine

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10.1016/j.biochi.2017.01.001

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title = "Medium throughput biochemical compound screening identifies novel agents for pharmacotherapy of neurofibromatosis type 1",

abstract = "The variable manifestation of phenotypes that occur in patients with neurofibromatosis type 1 (NF1) includes benign and malignant neurocutaneous tumors for which no adequate treatment exists. Cell-based screening of known bioactive compounds library identified the protein phosphatase 2A (PP2A) inhibitor Cantharidin and the L-type calcium channel blocker Nifedipine as potential candidates for NF1 pharmacotherapy. Validation of screening results using human NF1-associated malignant peripheral nerve sheath tumor (MPNST) cells showed that Cantharidin effectively impeded MPNST cell growth, while Nifedipine treatment significantly decreased local tumor growth in an MPNST xenograft animal model. These data suggest that inhibitors of PP2A, as well as calcium channel blockers, might be used in broader MPNST preclinical studies as single agents or in combinatorial therapeutic strategies.",

keywords = "Cantharidin, Chemical screening, Neurofibromatosis type 1, Nifedipine",

author = "Galina Semenova and Stepanova, {Dina S.} and Deyev, {Sergey M.} and Jonathan Chernoff",

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doi = "10.1016/j.biochi.2017.01.001",

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T1 - Medium throughput biochemical compound screening identifies novel agents for pharmacotherapy of neurofibromatosis type 1

AU - Semenova, Galina

AU - Stepanova, Dina S.

AU - Deyev, Sergey M.

AU - Chernoff, Jonathan

PY - 2017/4/1

Y1 - 2017/4/1

N2 - The variable manifestation of phenotypes that occur in patients with neurofibromatosis type 1 (NF1) includes benign and malignant neurocutaneous tumors for which no adequate treatment exists. Cell-based screening of known bioactive compounds library identified the protein phosphatase 2A (PP2A) inhibitor Cantharidin and the L-type calcium channel blocker Nifedipine as potential candidates for NF1 pharmacotherapy. Validation of screening results using human NF1-associated malignant peripheral nerve sheath tumor (MPNST) cells showed that Cantharidin effectively impeded MPNST cell growth, while Nifedipine treatment significantly decreased local tumor growth in an MPNST xenograft animal model. These data suggest that inhibitors of PP2A, as well as calcium channel blockers, might be used in broader MPNST preclinical studies as single agents or in combinatorial therapeutic strategies.

AB - The variable manifestation of phenotypes that occur in patients with neurofibromatosis type 1 (NF1) includes benign and malignant neurocutaneous tumors for which no adequate treatment exists. Cell-based screening of known bioactive compounds library identified the protein phosphatase 2A (PP2A) inhibitor Cantharidin and the L-type calcium channel blocker Nifedipine as potential candidates for NF1 pharmacotherapy. Validation of screening results using human NF1-associated malignant peripheral nerve sheath tumor (MPNST) cells showed that Cantharidin effectively impeded MPNST cell growth, while Nifedipine treatment significantly decreased local tumor growth in an MPNST xenograft animal model. These data suggest that inhibitors of PP2A, as well as calcium channel blockers, might be used in broader MPNST preclinical studies as single agents or in combinatorial therapeutic strategies.

KW - Cantharidin

KW - Chemical screening

KW - Neurofibromatosis type 1

KW - Nifedipine

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DO - 10.1016/j.biochi.2017.01.001

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JF - Biochimie

ER -

Medium throughput biochemical compound screening identifies novel agents for pharmacotherapy of neurofibromatosis type 1

Abstract

Keywords

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