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Article

A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib

  • Authors:
    • Azmi Yerlikaya
    • Elif Erdoğan
    • Emrah Okur
    • Şerife Yerlikaya
    • Bircan Savran
  • View Affiliations / Copyright

    Affiliations: Department of Medical Biology, Faculty of Medicine, Dumlupınar University, Kütahya 43100, Turkey, Department of Biology, Faculty of Arts and Sciences, Dumlupınar University, Kütahya 43100, Turkey, Department of Biochemistry, Faculty of Arts and Sciences, Dumlupınar University, Kütahya 43100, Turkey, Department of Pediatrics, Faculty of Medicine, Dumlupınar University, Kütahya 43100, Turkey
  • Pages: 323-330
    |
    Published online on: May 17, 2016
       https://doi.org/10.3892/ol.2016.4597
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Abstract

Glucose-regulated protein 78 kDa/binding immunoglobulin protein (GRP78/BIP) is a well-known endoplasmic reticulum (ER) chaperone protein regulating ER stress by facilitating protein folding, assembly and Ca2+ binding. GRP78 is also a member of the heat shock protein 70 gene family and induces tumor cell survival and resistance to chemotherapeutics. Bortezomib is a highly specific 26S proteasome inhibitor that has been approved as treatment for patients with multiple myeloma. The present study first examined the dose‑ and time‑dependent effects of bortezomib on GRP78 expression levels in the highly metastatic mouse breast cancer 4T1 cell line using western blot analysis. The analysis results revealed that GRP78 levels were significantly increased by bortezomib at a dose as low as 10 nM. Time‑dependent experiments indicated that the accumulation of GRP78 was initiated after a 24 h incubation period following the addition of 10 nM bortezomib. Subsequently, the present study determined the half maximal inhibitory concentration of intracellular calcium chelator BAPTA‑AM (13.6 µM) on 4T1 cells. The combination effect of BAPTA‑AM and bortezomib on the 4T1 cells was investigated using 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide and WST‑1 assays and an iCELLigence system. The results revealed that the combination of 10 nM bortezomib + 5 µM BAPTA‑AM is more cytotoxic compared with monotherapies, including 10 nM bortezomib, 1 µM BAPTA‑AM and 5 µM BAPTA‑AM. In addition, the present results revealed that bortezomib + BAPTA‑AM combination causes cell death through the induction of apoptosis. The present results also revealed that bortezomib + BAPTA‑AM combination‑induced apoptosis is associated with a clear increase in the phosphorylation of stress‑activated protein kinase/Jun amino‑terminal kinase SAPK/JNK. Overall, the present results suggest that bortezomib and BAPTA‑AM combination therapy may be a novel therapeutic strategy for breast cancer treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Yerlikaya A, Erdoğan E, Okur E, Yerlikaya Ş and Savran B: A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib. Oncol Lett 12: 323-330, 2016.
APA
Yerlikaya, A., Erdoğan, E., Okur, E., Yerlikaya, Ş., & Savran, B. (2016). A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib. Oncology Letters, 12, 323-330. https://doi.org/10.3892/ol.2016.4597
MLA
Yerlikaya, A., Erdoğan, E., Okur, E., Yerlikaya, Ş., Savran, B."A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib". Oncology Letters 12.1 (2016): 323-330.
Chicago
Yerlikaya, A., Erdoğan, E., Okur, E., Yerlikaya, Ş., Savran, B."A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib". Oncology Letters 12, no. 1 (2016): 323-330. https://doi.org/10.3892/ol.2016.4597
Copy and paste a formatted citation
x
Spandidos Publications style
Yerlikaya A, Erdoğan E, Okur E, Yerlikaya Ş and Savran B: A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib. Oncol Lett 12: 323-330, 2016.
APA
Yerlikaya, A., Erdoğan, E., Okur, E., Yerlikaya, Ş., & Savran, B. (2016). A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib. Oncology Letters, 12, 323-330. https://doi.org/10.3892/ol.2016.4597
MLA
Yerlikaya, A., Erdoğan, E., Okur, E., Yerlikaya, Ş., Savran, B."A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib". Oncology Letters 12.1 (2016): 323-330.
Chicago
Yerlikaya, A., Erdoğan, E., Okur, E., Yerlikaya, Ş., Savran, B."A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib". Oncology Letters 12, no. 1 (2016): 323-330. https://doi.org/10.3892/ol.2016.4597
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