Activation of over-expressed calcium channels as a potential therapeutic strategy for the treatment for breast cancer

Peters, Amelia A., Wu, Tina, Tan, Ping T., Roberts-Thomson, Sarah J. and Monteith, Gregory R. (2013). Activation of over-expressed calcium channels as a potential therapeutic strategy for the treatment for breast cancer. In: ASCEPT 2013: Abstracts. ASCEPT 2013: Annual Scientific Meeting, Melbourne, VIC, Australia, (128-128). 1-4 December, 2013.

Author Peters, Amelia A.
Wu, Tina
Tan, Ping T.
Roberts-Thomson, Sarah J.
Monteith, Gregory R.
Title of paper Activation of over-expressed calcium channels as a potential therapeutic strategy for the treatment for breast cancer
Conference name ASCEPT 2013: Annual Scientific Meeting
Conference location Melbourne, VIC, Australia
Conference dates 1-4 December, 2013
Proceedings title ASCEPT 2013: Abstracts
Place of Publication Hamilton Central, QLD, Australia
Publisher Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists
Publication Year 2013
Sub-type Published abstract
Open Access Status
Start page 128
End page 128
Total pages 1
Language eng
Formatted Abstract/Summary
Introduction. Elevated expression of calcium channels is a feature of some cancers including those of the breast. Numerous studies show that inhibition of some overexpressed calcium channels in cancer cells can inhibit proliferation and/or metastasis. Activation of over-expressed calcium channels is also suggested as an alternative strategy for the treatment of cancer, as increases in cytosolic free Ca2+ ([Ca2+]CYT) are associated with the induction of cell death, however, activation could potentially promote proliferation. A breast cancer cell line with inducible TRPV1 overexpression was used as a model to assess the potential for ion channel activators as therapies for breast cancer. TRPV1 is a calcium permeable ion channel that is activated by capsaicin, the hot component of chilli peppers.

Aims. To determine the relationship between TRPV1 expression and activation on the proliferation and viability of MCF7 breast cancer cells

Methods. Ca2+ assays using a fluorescent imaging plate reader (FLIPR) were used to assess Ca2+ responses to capsaicin in MCF7 cells with inducible TRPV1 expression (MCF7TRPV1). MTS assays were used to assess the effect of TRPV1 overexpression and capsaicin on proliferation and viability of MCF7TRPV1 cells. Cell death was assessed using propidium iodide and YO-PRO-1 staining. Real-time RT-PCR was used to evaluate mRNA levels.

Results. Capsaicin did not induce proliferation of MCF7TRPV1 cells at any level of TRPV1 expression. Capsaicin reduced the viability of MCF7TRPV1 cells at high TRPV1 expression levels in a concentration-dependent manner. Both over-expression and activation of TRPV1 were required to induce cell death. Capsaicin induced expression of the early response gene, c-fos, when TRPV1 expression was induced.

Discussion: These findings suggest that breast tumours that overexpress TRP channels may be therapeutically targeted using specific pharmacological activators.
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Conference Paper
Collection: School of Pharmacy Publications
 
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Created: Wed, 27 Aug 2014, 11:42:08 EST by Charna Kovacevic on behalf of School of Pharmacy