2-deoxy-D-glucose synergizes with doxorubicin or L-buthionine sulfoximine to reduce adhesion and migration of breast cancer cells

Ebtihal H. Mustafa, Huda T. Mahmoud, Mariam Y. Al-Hudhud, Maher Y Abdalla, Iman M Ahmad, Salem R. Yasin, Ali Z. Elkarmi, Lubna H. Tahtamouni

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Cancer metastasis depends on cell motility which is driven by cycles of actin polymerization and depolymerization. Reactive oxygen species (ROS) and metabolic oxidative stress have long been associated with cancer. ROS play a vital role in regulating actin dynamics that are sensitive to oxidative modification. The current work aimed at studying the effects of sub-lethal metabolic oxidative stress on actin cytoskeleton, focal adhesion and cell migration. Materials and Methods: T47D human breast cancer cells were treated with 2-deoxy-D-glucose (2DG), L-buthionine sulfoximine (BSO), or doxorubicin (DOX), individually or in combination, and changes in intracellular total glutathione and malondialdehyde (MDA) levels were measured. The expression of three major antioxidant enzymes was studied by immunoblotting, and cells were stained with fluorescent-phalloidin to evaluate changes in F-actin organization. In addition, cell adhesion and degradation ability were measured. Cell migration was studied using wound healing and transwell migration assays. Results: Our results show that treating T47D human breast cancer cells with drug combinations (2DG/BSO, 2DG/DOX, or BSO/DOX) decreased intracellular total glutathione and increased oxidized glutathione, lipid peroxidation, and cytotoxicity. In addition, the drug combinations caused a reduction in cell area and mitotic index, prophase arrest and a decreased ability to form invadopodia. The formation of F-actin aggregates was increased in treated T47D cells. Moreover, combination therapy reduced cell adhesion and the rate of cell migration. Conclusions: Our results suggest that exposure of T47D breast cancer cells to combination therapy reduces cell migration via effects on metabolic oxidative stress.

Original languageEnglish (US)
Pages (from-to)3213-3222
Number of pages10
JournalAsian Pacific Journal of Cancer Prevention
Volume16
Issue number8
DOIs
StatePublished - Jan 1 2015

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Buthionine Sulfoximine
Deoxyglucose
Doxorubicin
Cell Movement
Breast Neoplasms
Actins
Oxidative Stress
Drug Combinations
Cell Adhesion
Glutathione
Reactive Oxygen Species
Phalloidine
Prophase
Mitotic Index
Focal Adhesions
Glutathione Disulfide
Malondialdehyde
Actin Cytoskeleton
Immunoblotting
Polymerization

Keywords

  • F-actin
  • Focal adhesion
  • Glutathione
  • Metastasis
  • Oxidative stress

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Public Health, Environmental and Occupational Health
  • Cancer Research

Cite this

2-deoxy-D-glucose synergizes with doxorubicin or L-buthionine sulfoximine to reduce adhesion and migration of breast cancer cells. / Mustafa, Ebtihal H.; Mahmoud, Huda T.; Al-Hudhud, Mariam Y.; Abdalla, Maher Y; Ahmad, Iman M; Yasin, Salem R.; Elkarmi, Ali Z.; Tahtamouni, Lubna H.

In: Asian Pacific Journal of Cancer Prevention, Vol. 16, No. 8, 01.01.2015, p. 3213-3222.

Research output: Contribution to journalArticle

Mustafa, Ebtihal H. ; Mahmoud, Huda T. ; Al-Hudhud, Mariam Y. ; Abdalla, Maher Y ; Ahmad, Iman M ; Yasin, Salem R. ; Elkarmi, Ali Z. ; Tahtamouni, Lubna H. / 2-deoxy-D-glucose synergizes with doxorubicin or L-buthionine sulfoximine to reduce adhesion and migration of breast cancer cells. In: Asian Pacific Journal of Cancer Prevention. 2015 ; Vol. 16, No. 8. pp. 3213-3222.
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abstract = "Background: Cancer metastasis depends on cell motility which is driven by cycles of actin polymerization and depolymerization. Reactive oxygen species (ROS) and metabolic oxidative stress have long been associated with cancer. ROS play a vital role in regulating actin dynamics that are sensitive to oxidative modification. The current work aimed at studying the effects of sub-lethal metabolic oxidative stress on actin cytoskeleton, focal adhesion and cell migration. Materials and Methods: T47D human breast cancer cells were treated with 2-deoxy-D-glucose (2DG), L-buthionine sulfoximine (BSO), or doxorubicin (DOX), individually or in combination, and changes in intracellular total glutathione and malondialdehyde (MDA) levels were measured. The expression of three major antioxidant enzymes was studied by immunoblotting, and cells were stained with fluorescent-phalloidin to evaluate changes in F-actin organization. In addition, cell adhesion and degradation ability were measured. Cell migration was studied using wound healing and transwell migration assays. Results: Our results show that treating T47D human breast cancer cells with drug combinations (2DG/BSO, 2DG/DOX, or BSO/DOX) decreased intracellular total glutathione and increased oxidized glutathione, lipid peroxidation, and cytotoxicity. In addition, the drug combinations caused a reduction in cell area and mitotic index, prophase arrest and a decreased ability to form invadopodia. The formation of F-actin aggregates was increased in treated T47D cells. Moreover, combination therapy reduced cell adhesion and the rate of cell migration. Conclusions: Our results suggest that exposure of T47D breast cancer cells to combination therapy reduces cell migration via effects on metabolic oxidative stress.",
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T1 - 2-deoxy-D-glucose synergizes with doxorubicin or L-buthionine sulfoximine to reduce adhesion and migration of breast cancer cells

AU - Mustafa, Ebtihal H.

AU - Mahmoud, Huda T.

AU - Al-Hudhud, Mariam Y.

AU - Abdalla, Maher Y

AU - Ahmad, Iman M

AU - Yasin, Salem R.

AU - Elkarmi, Ali Z.

AU - Tahtamouni, Lubna H.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background: Cancer metastasis depends on cell motility which is driven by cycles of actin polymerization and depolymerization. Reactive oxygen species (ROS) and metabolic oxidative stress have long been associated with cancer. ROS play a vital role in regulating actin dynamics that are sensitive to oxidative modification. The current work aimed at studying the effects of sub-lethal metabolic oxidative stress on actin cytoskeleton, focal adhesion and cell migration. Materials and Methods: T47D human breast cancer cells were treated with 2-deoxy-D-glucose (2DG), L-buthionine sulfoximine (BSO), or doxorubicin (DOX), individually or in combination, and changes in intracellular total glutathione and malondialdehyde (MDA) levels were measured. The expression of three major antioxidant enzymes was studied by immunoblotting, and cells were stained with fluorescent-phalloidin to evaluate changes in F-actin organization. In addition, cell adhesion and degradation ability were measured. Cell migration was studied using wound healing and transwell migration assays. Results: Our results show that treating T47D human breast cancer cells with drug combinations (2DG/BSO, 2DG/DOX, or BSO/DOX) decreased intracellular total glutathione and increased oxidized glutathione, lipid peroxidation, and cytotoxicity. In addition, the drug combinations caused a reduction in cell area and mitotic index, prophase arrest and a decreased ability to form invadopodia. The formation of F-actin aggregates was increased in treated T47D cells. Moreover, combination therapy reduced cell adhesion and the rate of cell migration. Conclusions: Our results suggest that exposure of T47D breast cancer cells to combination therapy reduces cell migration via effects on metabolic oxidative stress.

AB - Background: Cancer metastasis depends on cell motility which is driven by cycles of actin polymerization and depolymerization. Reactive oxygen species (ROS) and metabolic oxidative stress have long been associated with cancer. ROS play a vital role in regulating actin dynamics that are sensitive to oxidative modification. The current work aimed at studying the effects of sub-lethal metabolic oxidative stress on actin cytoskeleton, focal adhesion and cell migration. Materials and Methods: T47D human breast cancer cells were treated with 2-deoxy-D-glucose (2DG), L-buthionine sulfoximine (BSO), or doxorubicin (DOX), individually or in combination, and changes in intracellular total glutathione and malondialdehyde (MDA) levels were measured. The expression of three major antioxidant enzymes was studied by immunoblotting, and cells were stained with fluorescent-phalloidin to evaluate changes in F-actin organization. In addition, cell adhesion and degradation ability were measured. Cell migration was studied using wound healing and transwell migration assays. Results: Our results show that treating T47D human breast cancer cells with drug combinations (2DG/BSO, 2DG/DOX, or BSO/DOX) decreased intracellular total glutathione and increased oxidized glutathione, lipid peroxidation, and cytotoxicity. In addition, the drug combinations caused a reduction in cell area and mitotic index, prophase arrest and a decreased ability to form invadopodia. The formation of F-actin aggregates was increased in treated T47D cells. Moreover, combination therapy reduced cell adhesion and the rate of cell migration. Conclusions: Our results suggest that exposure of T47D breast cancer cells to combination therapy reduces cell migration via effects on metabolic oxidative stress.

KW - F-actin

KW - Focal adhesion

KW - Glutathione

KW - Metastasis

KW - Oxidative stress

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