Inhibiting stemness and invasive properties of glioblastoma tumorsphere by combined treatment with temozolomide and a newly designed biguanide (HL156A)

Junjeong Choi, Ji Hyun Lee, Ilkyoo Koh, Jin Kyoung Shim, Junseong Park, Jeong Yong Jeon, Mijin Yun, Se Hoon Kim, Jong In Yook, Eui Hyun Kim, Jong Hee Chang, Sun Ho Kim, Yong Min Huh, Su Jae Lee, Michael Pollak, Pilnam Kim, Seok Gu Kang, Jae Ho Cheong

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Studies have investigated biguanide-derived agents for the treatment of cancers and have reported their effects against tumorspheres (TSs). The purpose of this study was determining the effects of HL156A, a newly designed biguanide with improved pharmacokinetics, on glioblastoma TSs (GMB TSs) and assess the feasibility of this drug as a new line of therapy against glioblastoma, alone or combined with a conventional therapeutic agent, temozolomide(TMZ). The effects of HL156A, alone and combined with TMZ, on the stemness and invasive properties of GBM TSs and survival of orthotopic xenograft animals were assessed. HL156A, combined with TMZ, inhibited the stemness of GBM TSs, proven by neurosphere formation assay and marker expression. Three-dimensional collagen matrix invasion assays provided evidence that combined treatment inhibited invasive properties, compared with control and TMZ-alone treatment groups. TMZ alone and combined treatment repressed the expression of epithelial-mesenchymal transition-related genes. A gene ontology comparison of TMZ and combination-treatment groups revealed altered expression of genes encoding proteins involved in cellular adhesion and migration. Combined treatment with HL156A and TMZ showed survival benefits in an orthotopic xenograft mouse model. The inhibitory effect of combination treatment on the stemness and invasive properties of GBM TSs suggest the potential usage of this regimen as a novel strategy for the treatment of GBM.

Original languageEnglish
Pages (from-to)65643-65659
Number of pages17
JournalOncotarget
Volume7
Issue number40
DOIs
Publication statusPublished - 2016 Jan 1

Fingerprint

temozolomide
Biguanides
Glioblastoma
Heterografts
Gene Ontology
Epithelial-Mesenchymal Transition
HL156A
Collagen

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Choi, Junjeong ; Lee, Ji Hyun ; Koh, Ilkyoo ; Shim, Jin Kyoung ; Park, Junseong ; Jeon, Jeong Yong ; Yun, Mijin ; Kim, Se Hoon ; Yook, Jong In ; Kim, Eui Hyun ; Chang, Jong Hee ; Kim, Sun Ho ; Huh, Yong Min ; Lee, Su Jae ; Pollak, Michael ; Kim, Pilnam ; Kang, Seok Gu ; Cheong, Jae Ho. / Inhibiting stemness and invasive properties of glioblastoma tumorsphere by combined treatment with temozolomide and a newly designed biguanide (HL156A). In: Oncotarget. 2016 ; Vol. 7, No. 40. pp. 65643-65659.
@article{8892f0e83b1c468ab7b923d435ee940f,
title = "Inhibiting stemness and invasive properties of glioblastoma tumorsphere by combined treatment with temozolomide and a newly designed biguanide (HL156A)",
abstract = "Studies have investigated biguanide-derived agents for the treatment of cancers and have reported their effects against tumorspheres (TSs). The purpose of this study was determining the effects of HL156A, a newly designed biguanide with improved pharmacokinetics, on glioblastoma TSs (GMB TSs) and assess the feasibility of this drug as a new line of therapy against glioblastoma, alone or combined with a conventional therapeutic agent, temozolomide(TMZ). The effects of HL156A, alone and combined with TMZ, on the stemness and invasive properties of GBM TSs and survival of orthotopic xenograft animals were assessed. HL156A, combined with TMZ, inhibited the stemness of GBM TSs, proven by neurosphere formation assay and marker expression. Three-dimensional collagen matrix invasion assays provided evidence that combined treatment inhibited invasive properties, compared with control and TMZ-alone treatment groups. TMZ alone and combined treatment repressed the expression of epithelial-mesenchymal transition-related genes. A gene ontology comparison of TMZ and combination-treatment groups revealed altered expression of genes encoding proteins involved in cellular adhesion and migration. Combined treatment with HL156A and TMZ showed survival benefits in an orthotopic xenograft mouse model. The inhibitory effect of combination treatment on the stemness and invasive properties of GBM TSs suggest the potential usage of this regimen as a novel strategy for the treatment of GBM.",
author = "Junjeong Choi and Lee, {Ji Hyun} and Ilkyoo Koh and Shim, {Jin Kyoung} and Junseong Park and Jeon, {Jeong Yong} and Mijin Yun and Kim, {Se Hoon} and Yook, {Jong In} and Kim, {Eui Hyun} and Chang, {Jong Hee} and Kim, {Sun Ho} and Huh, {Yong Min} and Lee, {Su Jae} and Michael Pollak and Pilnam Kim and Kang, {Seok Gu} and Cheong, {Jae Ho}",
year = "2016",
month = "1",
day = "1",
doi = "10.18632/oncotarget.11595",
language = "English",
volume = "7",
pages = "65643--65659",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "40",

}

Choi, J, Lee, JH, Koh, I, Shim, JK, Park, J, Jeon, JY, Yun, M, Kim, SH, Yook, JI, Kim, EH, Chang, JH, Kim, SH, Huh, YM, Lee, SJ, Pollak, M, Kim, P, Kang, SG & Cheong, JH 2016, 'Inhibiting stemness and invasive properties of glioblastoma tumorsphere by combined treatment with temozolomide and a newly designed biguanide (HL156A)', Oncotarget, vol. 7, no. 40, pp. 65643-65659. https://doi.org/10.18632/oncotarget.11595

Inhibiting stemness and invasive properties of glioblastoma tumorsphere by combined treatment with temozolomide and a newly designed biguanide (HL156A). / Choi, Junjeong; Lee, Ji Hyun; Koh, Ilkyoo; Shim, Jin Kyoung; Park, Junseong; Jeon, Jeong Yong; Yun, Mijin; Kim, Se Hoon; Yook, Jong In; Kim, Eui Hyun; Chang, Jong Hee; Kim, Sun Ho; Huh, Yong Min; Lee, Su Jae; Pollak, Michael; Kim, Pilnam; Kang, Seok Gu; Cheong, Jae Ho.

In: Oncotarget, Vol. 7, No. 40, 01.01.2016, p. 65643-65659.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inhibiting stemness and invasive properties of glioblastoma tumorsphere by combined treatment with temozolomide and a newly designed biguanide (HL156A)

AU - Choi, Junjeong

AU - Lee, Ji Hyun

AU - Koh, Ilkyoo

AU - Shim, Jin Kyoung

AU - Park, Junseong

AU - Jeon, Jeong Yong

AU - Yun, Mijin

AU - Kim, Se Hoon

AU - Yook, Jong In

AU - Kim, Eui Hyun

AU - Chang, Jong Hee

AU - Kim, Sun Ho

AU - Huh, Yong Min

AU - Lee, Su Jae

AU - Pollak, Michael

AU - Kim, Pilnam

AU - Kang, Seok Gu

AU - Cheong, Jae Ho

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Studies have investigated biguanide-derived agents for the treatment of cancers and have reported their effects against tumorspheres (TSs). The purpose of this study was determining the effects of HL156A, a newly designed biguanide with improved pharmacokinetics, on glioblastoma TSs (GMB TSs) and assess the feasibility of this drug as a new line of therapy against glioblastoma, alone or combined with a conventional therapeutic agent, temozolomide(TMZ). The effects of HL156A, alone and combined with TMZ, on the stemness and invasive properties of GBM TSs and survival of orthotopic xenograft animals were assessed. HL156A, combined with TMZ, inhibited the stemness of GBM TSs, proven by neurosphere formation assay and marker expression. Three-dimensional collagen matrix invasion assays provided evidence that combined treatment inhibited invasive properties, compared with control and TMZ-alone treatment groups. TMZ alone and combined treatment repressed the expression of epithelial-mesenchymal transition-related genes. A gene ontology comparison of TMZ and combination-treatment groups revealed altered expression of genes encoding proteins involved in cellular adhesion and migration. Combined treatment with HL156A and TMZ showed survival benefits in an orthotopic xenograft mouse model. The inhibitory effect of combination treatment on the stemness and invasive properties of GBM TSs suggest the potential usage of this regimen as a novel strategy for the treatment of GBM.

AB - Studies have investigated biguanide-derived agents for the treatment of cancers and have reported their effects against tumorspheres (TSs). The purpose of this study was determining the effects of HL156A, a newly designed biguanide with improved pharmacokinetics, on glioblastoma TSs (GMB TSs) and assess the feasibility of this drug as a new line of therapy against glioblastoma, alone or combined with a conventional therapeutic agent, temozolomide(TMZ). The effects of HL156A, alone and combined with TMZ, on the stemness and invasive properties of GBM TSs and survival of orthotopic xenograft animals were assessed. HL156A, combined with TMZ, inhibited the stemness of GBM TSs, proven by neurosphere formation assay and marker expression. Three-dimensional collagen matrix invasion assays provided evidence that combined treatment inhibited invasive properties, compared with control and TMZ-alone treatment groups. TMZ alone and combined treatment repressed the expression of epithelial-mesenchymal transition-related genes. A gene ontology comparison of TMZ and combination-treatment groups revealed altered expression of genes encoding proteins involved in cellular adhesion and migration. Combined treatment with HL156A and TMZ showed survival benefits in an orthotopic xenograft mouse model. The inhibitory effect of combination treatment on the stemness and invasive properties of GBM TSs suggest the potential usage of this regimen as a novel strategy for the treatment of GBM.

UR - http://www.scopus.com/inward/record.url?scp=84994193481&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994193481&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.11595

DO - 10.18632/oncotarget.11595

M3 - Article

C2 - 27582539

AN - SCOPUS:84994193481

VL - 7

SP - 65643

EP - 65659

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 40

ER -