A survey of human breast cancer sensitivity to growth inhibition by calmodulin antagonists in tissue culture

Strobl, Jeannine S.; Peterson, Virginia A.; Woodfork, Karen

doi:10.1016/0006-2952(94)90250-x

Cited by 19 publications

(6 citation statements)

References 20 publications

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“…Inhibition of CaM activity has been shown to result in the arrest of either the G 1 or G 2 /M phase of the cell cycle (40). Furthermore, it has been shown that human breast cancer cells are highly sensitive to the growth inhibitory actions of CaM antagonists (41). In MCF‐7 cells, the growth inhibitor effects of different CaM antagonists correlate with their antagonistic effects on CaM activity (42).…”

Section: Discussionmentioning

confidence: 99%

Modulation of intracellular calcium and calmodulin by melatonin in MCF‐7 human breast cancer cells

Dai

Inscho

Yuan

et al. 2002

Journal of Pineal Research

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The pineal hormone, melatonin, has been shown to inhibit the proliferation of the estrogen receptor alpha (ERalpha)-positive macrophage chemotactic factor (MCF)-7 human breast cancer cells. Previous studies from other systems indicate that melatonin modulates the calcium (Ca2+)/calmodulin (CaM) signaling pathway either by changing intracellular calcium concentration ([Ca2+]i) via activation of its G-protein coupled membrane receptors, or through a direct interaction with CaM. In this study, although melatonin alone had no effect on basal [Ca2+]i in MCF-7 cells, it significantly enhanced the elevation of [Ca2+]i induction by extracellular adenosine triphosphate (ATP), which increases [Ca2+]i via the G protein-coupled P2y-purinoceptor and the phospholipase C (PLC) pathway. Pretreatment of MCF-7 cells with 10(-7) M melatonin increased the 10(-5) M ATP-induced [Ca2+]i peak change from 79.4 +/- 11.6 nM to 146.2 +/- 22.3 nM. Furthermore, without changing total cellular CaM levels, melatonin markedly increased the amount of membrane-bound CaM to 237 and 162% of control levels after I and 6 hr of treatment, respectively. Cytosolic CaM levels were also elevated to 172% of control after 6 hr of melatonin treatment. Correlative growth studies demonstrated that ATP (10(-5) M) can stimulate MCF-7 cell growth, that melatonin can suppress MCF-7 cell proliferation, but that pretreatment of MCF-7 cells with melatonin followed by ATP(10(-5) M), like 10(-4) M ATP can further suppress MCF-7 cell proliferation; this indicates that melatonin's potentiation of ATP induced [Ca2+]i may be above the threshold for cell growth. Given the important role of [Ca2+]i and CaM in tumor cell homeostasis and proliferation and melatonin's modulation of [Ca2+]i, melatonin's effects on the Ca2+/CaM signaling pathway may play an important role in mediating the growth-inhibitory effect of melatonin on MCF-7 human breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

Modulation of intracellular calcium and calmodulin by melatonin in MCF‐7 human breast cancer cells

Dai

Inscho

Yuan

et al. 2002

Journal of Pineal Research

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“…This activity could participate in the therapeutic benefit associated with tamoxifen uptake. The possibility that Ca 2+ -dependent pathways could be involved was considered because (a) a recent study indicated that voltage-gated Ca 2+ channel antagonists potentiated the antiproliferative effects of tamoxifen (Gupta et al, 1994), (b) tamoxifen can interact with several Ca 2+ control elements including calmodulin (Strobl et al, 1994), and (c) E-cadherin/catenin functions are Ca 2+ dependent. In this work, we have demonstrated that the voltage-gated Ca 2+ channel antagonist, verapamil, and to a lesser extent, nifedipine, potentiated the effects of tamoxifen on E-cadherin/catenin functions.…”

Section: Discussionmentioning

confidence: 99%

“…Ca 2+ participates in the regulation of the Ecadherin/catenin complex. Furthermore, there are several studies indicating that Ca 2+ dependent pathways could be involved in the mechanisms of action of tamoxifen (Castoria et al, 1988;Strobl et al, 1994). These data prompted us to test the hypothesis that the restoration of the E-cadherin/catenin complex function induced by tamoxifen could be modulated by Ca 2+ modulators.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of tamoxifen-induced E-cadherin function by Ca2+ channel antagonists in human breast cancer MCF7/6 cells

Charlier

Bruyneel

Lechanteur

et al. 1996

European Journal of Pharmacology

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Despite its intensive use in adjuvant breast cancer therapy for more than 30 years, the exact mechanisms of action of tamoxifen have not yet been fully characterized. Tamoxifen was recently shown to restore the Ecadherin function of human breast cancer MCF7/6 cells and to suppress their invasive phenotype. Because tamoxifen interacts with targets implicated in Ca 2+ homeostasis, we explored the possibility that the restoration of E-cadherin function in MCF7/6 cells induced by this drug could be affected by Ca 2+ modulators. Two different Ca 2+ channel antagonists (verapamil and nifedipine) potentiated the effect of tamoxifen on E-cadherin function, as evaluated with a fast cell aggregation assay. These molecules decreased the tamoxifen concentration needed to restore the E-cadherin function from 10 -6 M to 10 -7 M. When incubated with a Ca 2+ channel agonist, Bay K8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methylphenyl)-pyridine-5-carboxylate), the effect of tamoxifen on E-cadherin function was completely abolished. These results demonstrate that the restoration of the E-cadherin function induced by tamoxifen depends, at least in part, on a Ca 2+ pathway, and support the evidence of an effect of tamoxifen on Ca 2+ -dependent mechanisms. Our data also suggest that Ca 2+ channel modulators could make it possible to decrease the dose of tamoxifen administered to patients without reducing the therapeutic effects.

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“…In some studies cells were depleted of E2 and staged to reduce basal Erk1/2 phosphorylation by maintaining them in PRF-DMEM, 2% charcoal-dextran stripped FBS [23] for 4 days with one medium change on day 2. In other studies cells were depleted of E2 and staged by maintaining them in serumfree medium, as described in figures.…”

Section: Cellular Staging and Protein Harvestingmentioning

confidence: 99%

“…To assess cell proliferation, MCF-7 cultures were plated in 6-well culture dishes at 1 × 10 5 cells/well and maintained in PRF-DMEM containing 2% charcoal-dextran stripped FBS [23] for 4 days with one medium change on day 2. For 6 consecutive days cells were completely re-fed PRF-DMEM, 2% stripped FBS and no additions (control), 3 nM E2 or 100 ng/mL EGF.…”

Section: Dna Assaymentioning

confidence: 99%

Difficulty demonstrating estradiol-mediated Erk1/2 phosphorylation in MCF-7 cells

Brower

Roberts

Antonini

et al. 2005

The Journal of Steroid Biochemistry and Molecular Biology

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A survey of human breast cancer sensitivity to growth inhibition by calmodulin antagonists in tissue culture

Cited by 19 publications

References 20 publications

Modulation of intracellular calcium and calmodulin by melatonin in MCF‐7 human breast cancer cells

Modulation of intracellular calcium and calmodulin by melatonin in MCF‐7 human breast cancer cells

Enhancement of tamoxifen-induced E-cadherin function by Ca2+ channel antagonists in human breast cancer MCF7/6 cells

Difficulty demonstrating estradiol-mediated Erk1/2 phosphorylation in MCF-7 cells

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