Monitoring the chemosensitizing effects of toremifene with flow cytometry in estrogen receptor negative multidrug resistant human breast cancer cells

W. Jeffrey Baker, Valerie J. Wiebe, Steven K. Koester, Vernon D. Emshoff, Juhani U. Maenpaa, Gregory T. Wurz, Michael W. DeGregorio

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The clinical study of compounds that modulate multidrug resistance in cancer cells has been hindered by both the toxicities of these agents and the inability to monitor their effectiveness at a cellular level. The non-steroidal triphenylethylene toremifene is well tolerated clinically and can sensitize multidrug resistant cells to the effects of doxorubicin in vitro. The chemosensitizing properties of toremifene in estrogen receptor negative, multidrug resistant MDA-A1 human breast cancer cells were studied using flow cytometric analysis. Cell cycle kinetics of MDA-A1 cells were not significantly affected by treatment with either toremifene or doxorubicin alone, as the majority of cells remained in G0/G1. However, preincubation with toremifene for 70 hours followed by treatment with doxorubicin caused a marked shift of cells to G2, as cells appeared to be blocked in that phase of the cell cycle. This result was nearly identical to the effect of doxorubicin alone on doxorubicin-sensitive MDA-MB-231 breast cancer cells and can be interpreted as a "resensitization" by toremifene of MDA-A1 cells to doxorubicin. This chemosensitizing effect of toremifene was accompanied by an enhanced accumulation of doxorubicin in MDA-A1 cells (+110% after 70 hours pre-incubation with toremifene), and by a depression in protein kinase C activity in MDA-A1 cells that was maximal following 70 hours incubation with toremifene. Flow cytometry is a widely available technique that might be applied clinically to monitor at the cellular level the chemosensitizing effects of toremifene and other modulators of multidrug resistance.

Original languageEnglish (US)
Pages (from-to)43-49
Number of pages7
JournalBreast Cancer Research and Treatment
Volume24
Issue number1
DOIs
StatePublished - Feb 1992
Externally publishedYes

Fingerprint

Toremifene
Estrogen Receptors
Flow Cytometry
Breast Neoplasms
Doxorubicin
Multiple Drug Resistance
Cell Cycle
Protein Kinase C

Keywords

  • flow cytometry
  • multidrug resistance
  • toremifene

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Monitoring the chemosensitizing effects of toremifene with flow cytometry in estrogen receptor negative multidrug resistant human breast cancer cells. / Baker, W. Jeffrey; Wiebe, Valerie J.; Koester, Steven K.; Emshoff, Vernon D.; Maenpaa, Juhani U.; Wurz, Gregory T.; DeGregorio, Michael W.

In: Breast Cancer Research and Treatment, Vol. 24, No. 1, 02.1992, p. 43-49.

Research output: Contribution to journalArticle

Baker, W. Jeffrey ; Wiebe, Valerie J. ; Koester, Steven K. ; Emshoff, Vernon D. ; Maenpaa, Juhani U. ; Wurz, Gregory T. ; DeGregorio, Michael W. / Monitoring the chemosensitizing effects of toremifene with flow cytometry in estrogen receptor negative multidrug resistant human breast cancer cells. In: Breast Cancer Research and Treatment. 1992 ; Vol. 24, No. 1. pp. 43-49.
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