Hypoxia re-programming oxygen nanobubbles sensitize human glioblastoma cells to temozolomide via methylation alterations

Pushpak Bhandari, Ouyang Lei, Joseph Maria Kumar Irudayaraj

Research output: Contribution to journalArticle

Abstract

Temozolomide (TMZ) treatment leads to antiangiogenesis and chemotherapeutic resistance in glioblastoma multiforme (GBM) by triggering hypoxia-adaptive pathways in the tumor microenvironment. There is a need for enhancing the effectiveness of TMZ treatment while reducing the cytotoxicity caused by the alkylating therapy. Here, we show that perturbation of the methylation levels and hypoxia-adaptive pathways in SF767 GBM cell lines using oxygen nanobubbles (NB) can significantly improve the effectiveness of TMZ treatment. We found that oxygen nanobubbles had a significant effect in increasing cell death and 5 mC methylation levels. Further, nanobubbles were found to localize intracellularly without any assistance from intracellular uptake ligands, indicating the potential of NB as an adjuvant to chemotherapeutics. A 30% increase in efficacy can be obtained using NB as an adjuvant to TMZ with the required TMZ dose. Thus, our elegant approach to utilize NB as a hypoxia and epigenetic pre-conditioning agent is expected to have a significant impact in glioblastoma therapy.

Original languageEnglish (US)
Pages (from-to)337-345
Number of pages9
JournalJournal of Bionanoscience
Volume11
Issue number5
DOIs
StatePublished - Oct 2017
Externally publishedYes

Fingerprint

temozolomide
Methylation
Glioblastoma
Oxygen
Cell death
Cytotoxicity
Tumors
Ligands
Cells
Tumor Microenvironment
Epigenomics
Cell Death
Hypoxia
Cell Line

Keywords

  • Epigenetics
  • Glioblastoma multiforme
  • Hypoxia
  • Oxygen nanobubbles
  • Temozolomide

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biomedical Engineering

Cite this

Hypoxia re-programming oxygen nanobubbles sensitize human glioblastoma cells to temozolomide via methylation alterations. / Bhandari, Pushpak; Lei, Ouyang; Irudayaraj, Joseph Maria Kumar.

In: Journal of Bionanoscience, Vol. 11, No. 5, 10.2017, p. 337-345.

Research output: Contribution to journalArticle

@article{8ec183c418da417b96b825502d9ded24,
title = "Hypoxia re-programming oxygen nanobubbles sensitize human glioblastoma cells to temozolomide via methylation alterations",
abstract = "Temozolomide (TMZ) treatment leads to antiangiogenesis and chemotherapeutic resistance in glioblastoma multiforme (GBM) by triggering hypoxia-adaptive pathways in the tumor microenvironment. There is a need for enhancing the effectiveness of TMZ treatment while reducing the cytotoxicity caused by the alkylating therapy. Here, we show that perturbation of the methylation levels and hypoxia-adaptive pathways in SF767 GBM cell lines using oxygen nanobubbles (NB) can significantly improve the effectiveness of TMZ treatment. We found that oxygen nanobubbles had a significant effect in increasing cell death and 5 mC methylation levels. Further, nanobubbles were found to localize intracellularly without any assistance from intracellular uptake ligands, indicating the potential of NB as an adjuvant to chemotherapeutics. A 30{\%} increase in efficacy can be obtained using NB as an adjuvant to TMZ with the required TMZ dose. Thus, our elegant approach to utilize NB as a hypoxia and epigenetic pre-conditioning agent is expected to have a significant impact in glioblastoma therapy.",
keywords = "Epigenetics, Glioblastoma multiforme, Hypoxia, Oxygen nanobubbles, Temozolomide",
author = "Pushpak Bhandari and Ouyang Lei and Irudayaraj, {Joseph Maria Kumar}",
year = "2017",
month = "10",
doi = "10.1166/jbns.2017.1450",
language = "English (US)",
volume = "11",
pages = "337--345",
journal = "Journal of Bionanoscience",
issn = "1557-7910",
publisher = "American Scientific Publishers",
number = "5",

}

TY - JOUR

T1 - Hypoxia re-programming oxygen nanobubbles sensitize human glioblastoma cells to temozolomide via methylation alterations

AU - Bhandari, Pushpak

AU - Lei, Ouyang

AU - Irudayaraj, Joseph Maria Kumar

PY - 2017/10

Y1 - 2017/10

N2 - Temozolomide (TMZ) treatment leads to antiangiogenesis and chemotherapeutic resistance in glioblastoma multiforme (GBM) by triggering hypoxia-adaptive pathways in the tumor microenvironment. There is a need for enhancing the effectiveness of TMZ treatment while reducing the cytotoxicity caused by the alkylating therapy. Here, we show that perturbation of the methylation levels and hypoxia-adaptive pathways in SF767 GBM cell lines using oxygen nanobubbles (NB) can significantly improve the effectiveness of TMZ treatment. We found that oxygen nanobubbles had a significant effect in increasing cell death and 5 mC methylation levels. Further, nanobubbles were found to localize intracellularly without any assistance from intracellular uptake ligands, indicating the potential of NB as an adjuvant to chemotherapeutics. A 30% increase in efficacy can be obtained using NB as an adjuvant to TMZ with the required TMZ dose. Thus, our elegant approach to utilize NB as a hypoxia and epigenetic pre-conditioning agent is expected to have a significant impact in glioblastoma therapy.

AB - Temozolomide (TMZ) treatment leads to antiangiogenesis and chemotherapeutic resistance in glioblastoma multiforme (GBM) by triggering hypoxia-adaptive pathways in the tumor microenvironment. There is a need for enhancing the effectiveness of TMZ treatment while reducing the cytotoxicity caused by the alkylating therapy. Here, we show that perturbation of the methylation levels and hypoxia-adaptive pathways in SF767 GBM cell lines using oxygen nanobubbles (NB) can significantly improve the effectiveness of TMZ treatment. We found that oxygen nanobubbles had a significant effect in increasing cell death and 5 mC methylation levels. Further, nanobubbles were found to localize intracellularly without any assistance from intracellular uptake ligands, indicating the potential of NB as an adjuvant to chemotherapeutics. A 30% increase in efficacy can be obtained using NB as an adjuvant to TMZ with the required TMZ dose. Thus, our elegant approach to utilize NB as a hypoxia and epigenetic pre-conditioning agent is expected to have a significant impact in glioblastoma therapy.

KW - Epigenetics

KW - Glioblastoma multiforme

KW - Hypoxia

KW - Oxygen nanobubbles

KW - Temozolomide

UR - http://www.scopus.com/inward/record.url?scp=85028756814&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028756814&partnerID=8YFLogxK

U2 - 10.1166/jbns.2017.1450

DO - 10.1166/jbns.2017.1450

M3 - Article

AN - SCOPUS:85028756814

VL - 11

SP - 337

EP - 345

JO - Journal of Bionanoscience

JF - Journal of Bionanoscience

SN - 1557-7910

IS - 5

ER -