The SR-B1 Receptor as a Potential Target for Treating Glioblastoma

Ethan Berney, Nirupama Sabnis, Marlyn Panchoo, Sangram Limbaji Raut, Rob Dickerman, Andras G. Lacko

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Purpose. The goal of these studies was to provide proof of concept for a novel targeted therapy for Glioblastoma Multiforme (GBM). Methods. These studies involve the evaluation of reconstituted high density lipoprotein (rHDL) nanoparticles (NPs) as delivery agents for the drug, mammalian Target of Rapamycin (mTOR) inhibitor Everolimus (EVR) to GBM cells. Cytotoxicity studies and assessment of downstream effects, including apoptosis, migration, and cell cycle events, were probed, in relation to the expression of scavenger receptor B type 1 (SR-B1) by GBM cells. Results. Findings from cytotoxicity studies indicate that the rHDL/EVR formulation was 185 times more potent than free EVR against high SR-B1 expressing cell line (LN 229). Cell cycle analysis revealed that rHDL/EVR treated LN229 cells had a 5.8 times higher apoptotic cell population than those treated with EVR. The sensitivity of GBM cells to EVR treatment was strongly correlated with SR-B1 expression. Conclusions. These studies present strong proof of concept regarding the efficacy of delivering EVR and likely other agents, via a biocompatible transport system, targeted to the SR-B1 receptor that is upregulated in most cancers, including GBM. Targeting the SR-B1 receptor could thus lead to effective personalized therapy of GBM.

Original languageEnglish
Article number1805841
JournalJournal of Oncology
Volume2019
DOIs
StatePublished - 1 Jan 2019

Fingerprint

Scavenger Receptors
Glioblastoma
HDL Lipoproteins
Cell Cycle
Sirolimus
Everolimus
Nanoparticles
Apoptosis
Cell Line
Therapeutics
Pharmaceutical Preparations
Population

Cite this

Berney, E., Sabnis, N., Panchoo, M., Raut, S. L., Dickerman, R., & Lacko, A. G. (2019). The SR-B1 Receptor as a Potential Target for Treating Glioblastoma. Journal of Oncology, 2019, [1805841]. https://doi.org/10.1155/2019/1805841
Berney, Ethan ; Sabnis, Nirupama ; Panchoo, Marlyn ; Raut, Sangram Limbaji ; Dickerman, Rob ; Lacko, Andras G. / The SR-B1 Receptor as a Potential Target for Treating Glioblastoma. In: Journal of Oncology. 2019 ; Vol. 2019.
@article{42d5302c89f74fd192929f1d1e9a5f80,
title = "The SR-B1 Receptor as a Potential Target for Treating Glioblastoma",
abstract = "Purpose. The goal of these studies was to provide proof of concept for a novel targeted therapy for Glioblastoma Multiforme (GBM). Methods. These studies involve the evaluation of reconstituted high density lipoprotein (rHDL) nanoparticles (NPs) as delivery agents for the drug, mammalian Target of Rapamycin (mTOR) inhibitor Everolimus (EVR) to GBM cells. Cytotoxicity studies and assessment of downstream effects, including apoptosis, migration, and cell cycle events, were probed, in relation to the expression of scavenger receptor B type 1 (SR-B1) by GBM cells. Results. Findings from cytotoxicity studies indicate that the rHDL/EVR formulation was 185 times more potent than free EVR against high SR-B1 expressing cell line (LN 229). Cell cycle analysis revealed that rHDL/EVR treated LN229 cells had a 5.8 times higher apoptotic cell population than those treated with EVR. The sensitivity of GBM cells to EVR treatment was strongly correlated with SR-B1 expression. Conclusions. These studies present strong proof of concept regarding the efficacy of delivering EVR and likely other agents, via a biocompatible transport system, targeted to the SR-B1 receptor that is upregulated in most cancers, including GBM. Targeting the SR-B1 receptor could thus lead to effective personalized therapy of GBM.",
author = "Ethan Berney and Nirupama Sabnis and Marlyn Panchoo and Raut, {Sangram Limbaji} and Rob Dickerman and Lacko, {Andras G.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1155/2019/1805841",
language = "English",
volume = "2019",
journal = "Journal of Oncology",
issn = "1687-8450",
publisher = "Hindawi Publishing Corporation",

}

Berney, E, Sabnis, N, Panchoo, M, Raut, SL, Dickerman, R & Lacko, AG 2019, 'The SR-B1 Receptor as a Potential Target for Treating Glioblastoma', Journal of Oncology, vol. 2019, 1805841. https://doi.org/10.1155/2019/1805841

The SR-B1 Receptor as a Potential Target for Treating Glioblastoma. / Berney, Ethan; Sabnis, Nirupama; Panchoo, Marlyn; Raut, Sangram Limbaji; Dickerman, Rob; Lacko, Andras G.

In: Journal of Oncology, Vol. 2019, 1805841, 01.01.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The SR-B1 Receptor as a Potential Target for Treating Glioblastoma

AU - Berney, Ethan

AU - Sabnis, Nirupama

AU - Panchoo, Marlyn

AU - Raut, Sangram Limbaji

AU - Dickerman, Rob

AU - Lacko, Andras G.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose. The goal of these studies was to provide proof of concept for a novel targeted therapy for Glioblastoma Multiforme (GBM). Methods. These studies involve the evaluation of reconstituted high density lipoprotein (rHDL) nanoparticles (NPs) as delivery agents for the drug, mammalian Target of Rapamycin (mTOR) inhibitor Everolimus (EVR) to GBM cells. Cytotoxicity studies and assessment of downstream effects, including apoptosis, migration, and cell cycle events, were probed, in relation to the expression of scavenger receptor B type 1 (SR-B1) by GBM cells. Results. Findings from cytotoxicity studies indicate that the rHDL/EVR formulation was 185 times more potent than free EVR against high SR-B1 expressing cell line (LN 229). Cell cycle analysis revealed that rHDL/EVR treated LN229 cells had a 5.8 times higher apoptotic cell population than those treated with EVR. The sensitivity of GBM cells to EVR treatment was strongly correlated with SR-B1 expression. Conclusions. These studies present strong proof of concept regarding the efficacy of delivering EVR and likely other agents, via a biocompatible transport system, targeted to the SR-B1 receptor that is upregulated in most cancers, including GBM. Targeting the SR-B1 receptor could thus lead to effective personalized therapy of GBM.

AB - Purpose. The goal of these studies was to provide proof of concept for a novel targeted therapy for Glioblastoma Multiforme (GBM). Methods. These studies involve the evaluation of reconstituted high density lipoprotein (rHDL) nanoparticles (NPs) as delivery agents for the drug, mammalian Target of Rapamycin (mTOR) inhibitor Everolimus (EVR) to GBM cells. Cytotoxicity studies and assessment of downstream effects, including apoptosis, migration, and cell cycle events, were probed, in relation to the expression of scavenger receptor B type 1 (SR-B1) by GBM cells. Results. Findings from cytotoxicity studies indicate that the rHDL/EVR formulation was 185 times more potent than free EVR against high SR-B1 expressing cell line (LN 229). Cell cycle analysis revealed that rHDL/EVR treated LN229 cells had a 5.8 times higher apoptotic cell population than those treated with EVR. The sensitivity of GBM cells to EVR treatment was strongly correlated with SR-B1 expression. Conclusions. These studies present strong proof of concept regarding the efficacy of delivering EVR and likely other agents, via a biocompatible transport system, targeted to the SR-B1 receptor that is upregulated in most cancers, including GBM. Targeting the SR-B1 receptor could thus lead to effective personalized therapy of GBM.

UR - http://www.scopus.com/inward/record.url?scp=85067653683&partnerID=8YFLogxK

U2 - 10.1155/2019/1805841

DO - 10.1155/2019/1805841

M3 - Article

VL - 2019

JO - Journal of Oncology

JF - Journal of Oncology

SN - 1687-8450

M1 - 1805841

ER -