Open Access

Activation of the CRABPII/RAR pathway by curcumin induces retinoic acid mediated apoptosis in retinoic acid resistant breast cancer cells

  • Authors:
    • Padmamalini Thulasiraman
    • Galen Garriga
    • Veena Danthuluri
    • Daniel J. McAndrews
    • Imran Q. Mohiuddin
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  • Published online on: March 8, 2017     https://doi.org/10.3892/or.2017.5495
  • Pages: 2007-2015
  • Copyright: © Thulasiraman et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Due to the anti-proliferative and anti-apoptotic effects of retinoic acid (RA), this hormone has emerged as a target for several diseases, including cancer. However, development of retinoid resistance is a critical issue and efforts to understand the retinoid signaling pathway may identify useful biomarkers for future clinical trials. Apoptotic responses of RA are exhibited through the cellular RA-binding protein II (CRABPII)/retinoic acid receptor (RAR) signaling cascade. Delivery of RA to RAR by CRABPII enhances the transcriptional activity of genes involved in cell death and cell cycle arrest. The purpose of this study was to investigate the role of curcumin in sensitizing RA-resistant triple-negative breast cancer (TNBC) cells to RA-mediated apoptosis. We provide evidence that curcumin upregulates the expression of CRABPII, RARβ and RARγ in two different TNBC cell lines. Co-treatment of the cells with curcumin and RA results in increased apoptosis as demonstrated by elevated cleavage of poly(ADP-ribose) polymerase and cleaved caspase-9. Additionally, silencing CRABPII reverses curcumin sensitization of TNBC cells to the apoptotic inducing effects of RA. These findings provide mechanistic insights into sensitizing TNBC cells to RA-mediated cell death by curcumin-induced upregulation of the CRABPII/RAR pathway.
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April-2017
Volume 37 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Thulasiraman P, Garriga G, Danthuluri V, McAndrews DJ and Mohiuddin IQ: Activation of the CRABPII/RAR pathway by curcumin induces retinoic acid mediated apoptosis in retinoic acid resistant breast cancer cells. Oncol Rep 37: 2007-2015, 2017
APA
Thulasiraman, P., Garriga, G., Danthuluri, V., McAndrews, D.J., & Mohiuddin, I.Q. (2017). Activation of the CRABPII/RAR pathway by curcumin induces retinoic acid mediated apoptosis in retinoic acid resistant breast cancer cells. Oncology Reports, 37, 2007-2015. https://doi.org/10.3892/or.2017.5495
MLA
Thulasiraman, P., Garriga, G., Danthuluri, V., McAndrews, D. J., Mohiuddin, I. Q."Activation of the CRABPII/RAR pathway by curcumin induces retinoic acid mediated apoptosis in retinoic acid resistant breast cancer cells". Oncology Reports 37.4 (2017): 2007-2015.
Chicago
Thulasiraman, P., Garriga, G., Danthuluri, V., McAndrews, D. J., Mohiuddin, I. Q."Activation of the CRABPII/RAR pathway by curcumin induces retinoic acid mediated apoptosis in retinoic acid resistant breast cancer cells". Oncology Reports 37, no. 4 (2017): 2007-2015. https://doi.org/10.3892/or.2017.5495