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Consequences of pharmacological inhibition of store-operated calcium entry on calcium signalling in MDA-MB- 468 breast cancer cells


Poo, GXH and Azimi, I and Roberts-Thomson, SJ and Monteith, GR, Consequences of pharmacological inhibition of store-operated calcium entry on calcium signalling in MDA-MB- 468 breast cancer cells, Proceedings of the APSA-ASCEPT Joint Scientific Meeting 2017, 5-8 December 2017, Brisbane, Australia, pp. 18. (2017) [Conference Extract]

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Introduction: Store-operated calcium entry (SOCE), describes the process whereby there is an influx of calcium ions (Ca2+) after intracellular Ca2+ stores are depleted. A remodelling of the molecular components of SOCE is evident in breast cancers of the poor prognosis basal molecular subtype. However, pharmacological studies of this pathway in breast cancer cells have often used non-specific SOCE inhibitors, non-physiological mechanisms of calcium store depletion and just one basal breast cancer cell line - MDA-MB-231.

Aims: To assess the effects of the selective SOCE inhibitors YM-58483 and Synta66 on calcium influx mediated by the Ca2+ store pump inhibitor cyclopiazonic acid (CPA), the purinergic receptor activator adenosine triphosphate (ATP), the protease-activated receptor-2 (PAR-2) activator trypsin and epidermal growth factor (EGF) in MDA-MB-468 basal breast cancer cells in the presence of extracellular Ca2+.

Methods: MDA-MB-468 cells were loaded with the Ca2+ sensitive indicator Fluo-4 and cytosolic free Ca2+ levels ([Ca2+]CYT) were assessed during treatment with CPA, ATP, trypsin and EGF in the absence or presence of YM-58483 or Synta66 using a Fluorescence Imaging Plate Reader (FLIPR).

Results: CPA, ATP, trypsin and EGF exhibited [Ca2+]CYT transients with different degrees of sustained Ca2+ influx. The effects of Synta66 and YM-58483 were greatest for CPA and ATP mediated Ca2+ influx. Sustained Ca2+ influx after stimulation was reduced by 35.1 and 35.5% for CPA (10 μM) and 52.4 and 48.6% for ATP (10 μM) by Synta66 and YM-58483, respectively.

Discussion: These studies define a role for SOCE as a consequence of activation in the regulation of sustained Ca 2+ influx in MDA-MB-468 basal breast cancer cells.

Item Details

Item Type:Conference Extract
Keywords:store-operated calcium entry, breast cancer
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Basic pharmacology
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the health sciences
UTAS Author:Azimi, I (Dr Iman Azimi)
ID Code:151231
Year Published:2017
Deposited By:Pharmacy
Deposited On:2022-07-25
Last Modified:2022-07-28

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