Effect of vitamin E on tamoxifen-treated breast cancer cells

Elizabeth A. Peralta, Melita L. Viegas, Somaja Louis, Deborah L. Engle, Gary Dunnington

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background: Induction of apoptosis by tamoxifen has been postulated to involve oxidative stress. Tamoxifen (TAM) may act on estrogen receptors (ER) located in the plasma membrane. Our hypothesis that supplemental antioxidant vitamin E (α-tocopherol) acts at the plasma membrane to alter the effectiveness of tamoxifen was tested in ER-positive breast cancer cell lines, MCF-7 and T47D. Methods: Cells were treated in vitro with 20-μM TAM alone and in combination with 10-μM α-tocopherol (AT). Estrogen growth signals were quantified by immunohistochemical staining for the mitogen-activated protein kinase p-ERK. Rapid changes in intracellular calcium were detected in TAM-treated MCF-7 and T-47D cells by fluorescence microscopy of cells loaded with the calcium-sensitive dye Fluo 4AM. Apoptosis was assayed by flow cytometry. Results: Proliferating cells in normal medium exhibited strong p-ERK staining. Addition of TAM abolished p-ERK staining and caused cell rounding and death. The addition of AT led to the restoration of cell proliferation and p-ERK expression even in the presence of high-dose TAM. Intracellular calcium rapidly increased in MCF-7 and T47D cells upon exposure to TAM, followed by an increase in caspase activation and eventual apoptosis. The increase in intracellular calcium was abolished by the addition of 10μM AT to TAM, and pan-caspase staining decreased at 5 hours from 72% to 41%. Conclusions: These studies suggest that supplemental vitamin E decreases the inhibitory effect of TAM on the proliferation of ER+ breast cancer cells and eliminates the rapid rise in intracellular calcium that leads to apoptosis stimulated by TAM. The use of vitamin E acetate supplements may be inadvisable for women taking tamoxifen.

Original languageEnglish (US)
Pages (from-to)607-615
Number of pages9
JournalSurgery
Volume140
Issue number4
DOIs
StatePublished - Oct 2006
Externally publishedYes

Fingerprint

Tamoxifen
Vitamin E
Breast Neoplasms
Calcium
Estrogen Receptors
Apoptosis
Staining and Labeling
Tocopherols
Caspases
Cell Membrane
MCF-7 Cells
Mitogen-Activated Protein Kinases
Fluorescence Microscopy
Flow Cytometry
Estrogens
Acetates
Oxidative Stress
Cell Death
Coloring Agents
Antioxidants

ASJC Scopus subject areas

  • Surgery

Cite this

Effect of vitamin E on tamoxifen-treated breast cancer cells. / Peralta, Elizabeth A.; Viegas, Melita L.; Louis, Somaja; Engle, Deborah L.; Dunnington, Gary.

In: Surgery, Vol. 140, No. 4, 10.2006, p. 607-615.

Research output: Contribution to journalArticle

Peralta, EA, Viegas, ML, Louis, S, Engle, DL & Dunnington, G 2006, 'Effect of vitamin E on tamoxifen-treated breast cancer cells', Surgery, vol. 140, no. 4, pp. 607-615. https://doi.org/10.1016/j.surg.2006.07.007
Peralta, Elizabeth A. ; Viegas, Melita L. ; Louis, Somaja ; Engle, Deborah L. ; Dunnington, Gary. / Effect of vitamin E on tamoxifen-treated breast cancer cells. In: Surgery. 2006 ; Vol. 140, No. 4. pp. 607-615.
@article{769f026516874e0c8ba4d36eea7f6d3c,
title = "Effect of vitamin E on tamoxifen-treated breast cancer cells",
abstract = "Background: Induction of apoptosis by tamoxifen has been postulated to involve oxidative stress. Tamoxifen (TAM) may act on estrogen receptors (ER) located in the plasma membrane. Our hypothesis that supplemental antioxidant vitamin E (α-tocopherol) acts at the plasma membrane to alter the effectiveness of tamoxifen was tested in ER-positive breast cancer cell lines, MCF-7 and T47D. Methods: Cells were treated in vitro with 20-μM TAM alone and in combination with 10-μM α-tocopherol (AT). Estrogen growth signals were quantified by immunohistochemical staining for the mitogen-activated protein kinase p-ERK. Rapid changes in intracellular calcium were detected in TAM-treated MCF-7 and T-47D cells by fluorescence microscopy of cells loaded with the calcium-sensitive dye Fluo 4AM. Apoptosis was assayed by flow cytometry. Results: Proliferating cells in normal medium exhibited strong p-ERK staining. Addition of TAM abolished p-ERK staining and caused cell rounding and death. The addition of AT led to the restoration of cell proliferation and p-ERK expression even in the presence of high-dose TAM. Intracellular calcium rapidly increased in MCF-7 and T47D cells upon exposure to TAM, followed by an increase in caspase activation and eventual apoptosis. The increase in intracellular calcium was abolished by the addition of 10μM AT to TAM, and pan-caspase staining decreased at 5 hours from 72{\%} to 41{\%}. Conclusions: These studies suggest that supplemental vitamin E decreases the inhibitory effect of TAM on the proliferation of ER+ breast cancer cells and eliminates the rapid rise in intracellular calcium that leads to apoptosis stimulated by TAM. The use of vitamin E acetate supplements may be inadvisable for women taking tamoxifen.",
author = "Peralta, {Elizabeth A.} and Viegas, {Melita L.} and Somaja Louis and Engle, {Deborah L.} and Gary Dunnington",
year = "2006",
month = "10",
doi = "10.1016/j.surg.2006.07.007",
language = "English (US)",
volume = "140",
pages = "607--615",
journal = "Surgery",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "4",

}

TY - JOUR

T1 - Effect of vitamin E on tamoxifen-treated breast cancer cells

AU - Peralta, Elizabeth A.

AU - Viegas, Melita L.

AU - Louis, Somaja

AU - Engle, Deborah L.

AU - Dunnington, Gary

PY - 2006/10

Y1 - 2006/10

N2 - Background: Induction of apoptosis by tamoxifen has been postulated to involve oxidative stress. Tamoxifen (TAM) may act on estrogen receptors (ER) located in the plasma membrane. Our hypothesis that supplemental antioxidant vitamin E (α-tocopherol) acts at the plasma membrane to alter the effectiveness of tamoxifen was tested in ER-positive breast cancer cell lines, MCF-7 and T47D. Methods: Cells were treated in vitro with 20-μM TAM alone and in combination with 10-μM α-tocopherol (AT). Estrogen growth signals were quantified by immunohistochemical staining for the mitogen-activated protein kinase p-ERK. Rapid changes in intracellular calcium were detected in TAM-treated MCF-7 and T-47D cells by fluorescence microscopy of cells loaded with the calcium-sensitive dye Fluo 4AM. Apoptosis was assayed by flow cytometry. Results: Proliferating cells in normal medium exhibited strong p-ERK staining. Addition of TAM abolished p-ERK staining and caused cell rounding and death. The addition of AT led to the restoration of cell proliferation and p-ERK expression even in the presence of high-dose TAM. Intracellular calcium rapidly increased in MCF-7 and T47D cells upon exposure to TAM, followed by an increase in caspase activation and eventual apoptosis. The increase in intracellular calcium was abolished by the addition of 10μM AT to TAM, and pan-caspase staining decreased at 5 hours from 72% to 41%. Conclusions: These studies suggest that supplemental vitamin E decreases the inhibitory effect of TAM on the proliferation of ER+ breast cancer cells and eliminates the rapid rise in intracellular calcium that leads to apoptosis stimulated by TAM. The use of vitamin E acetate supplements may be inadvisable for women taking tamoxifen.

AB - Background: Induction of apoptosis by tamoxifen has been postulated to involve oxidative stress. Tamoxifen (TAM) may act on estrogen receptors (ER) located in the plasma membrane. Our hypothesis that supplemental antioxidant vitamin E (α-tocopherol) acts at the plasma membrane to alter the effectiveness of tamoxifen was tested in ER-positive breast cancer cell lines, MCF-7 and T47D. Methods: Cells were treated in vitro with 20-μM TAM alone and in combination with 10-μM α-tocopherol (AT). Estrogen growth signals were quantified by immunohistochemical staining for the mitogen-activated protein kinase p-ERK. Rapid changes in intracellular calcium were detected in TAM-treated MCF-7 and T-47D cells by fluorescence microscopy of cells loaded with the calcium-sensitive dye Fluo 4AM. Apoptosis was assayed by flow cytometry. Results: Proliferating cells in normal medium exhibited strong p-ERK staining. Addition of TAM abolished p-ERK staining and caused cell rounding and death. The addition of AT led to the restoration of cell proliferation and p-ERK expression even in the presence of high-dose TAM. Intracellular calcium rapidly increased in MCF-7 and T47D cells upon exposure to TAM, followed by an increase in caspase activation and eventual apoptosis. The increase in intracellular calcium was abolished by the addition of 10μM AT to TAM, and pan-caspase staining decreased at 5 hours from 72% to 41%. Conclusions: These studies suggest that supplemental vitamin E decreases the inhibitory effect of TAM on the proliferation of ER+ breast cancer cells and eliminates the rapid rise in intracellular calcium that leads to apoptosis stimulated by TAM. The use of vitamin E acetate supplements may be inadvisable for women taking tamoxifen.

UR - http://www.scopus.com/inward/record.url?scp=33748983219&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748983219&partnerID=8YFLogxK

U2 - 10.1016/j.surg.2006.07.007

DO - 10.1016/j.surg.2006.07.007

M3 - Article

VL - 140

SP - 607

EP - 615

JO - Surgery

JF - Surgery

SN - 0039-6060

IS - 4

ER -