Amino Acids

pp 1–25 | Cite as

Curcumin inhibits autocrine growth hormone-mediated invasion and metastasis by targeting NF-κB signaling and polyamine metabolism in breast cancer cells

  • Ajda Coker-Gurkan
  • Merve Celik
  • Merve Ugur
  • Elif-Damla Arisan
  • Pinar Obakan-Yerlikaya
  • Zeynep Begum Durdu
  • Narcin Palavan-Unsal
Original Article

Abstract

Curcumin is assumed to be a plant-derived therapeutic drug that triggers apoptotic cell death in vitro and in vivo by affecting different molecular targets such as NF-κB. Phase I/II trial of curcumin alone or with chemotherapeutic drugs has been accomplished in pancreatic, colon, prostate and breast cancer cases. Recently, autocrine growth hormone (GH) signaling-induced cell growth, metastasis and drug resistance have been demonstrated in breast cancer. In this study, our aim was to investigate the potential therapeutic effect of curcumin by evaluating the molecular machinery of curcumin-triggered apoptotic cell death via focusing on NF-κB signaling and polyamine (PA) metabolism in autocrine GH-expressing MCF-7, MDA-MB-453 and MDA-MB-231 breast cancer cells. For this purpose, a pcDNA3.1 (+) vector with a GH gene insert was transfected by a liposomal agent in all breast cancer cells and then selection was conducted in neomycin (G418) included media. Autocrine GH-induced curcumin resistance was overcome in a dose-dependent manner and curcumin inhibited cell proliferation, invasion–metastasis and phosphorylation of p65 (Ser536), and thereby partly prevented its DNA binding activity in breast cancer cells. Moreover, curcumin induced caspase-mediated apoptotic cell death by activating the PA catabolic enzyme expressions, which led to generation of toxic by-products such as H2O2 in MCF-7, MDA-MB-453 and MDA-MB-231 GH+ breast cancer cells. In addition, transient silencing of SSAT prevented curcumin-induced cell viability loss and apoptotic cell death in each breast cancer cells. In conclusion, curcumin could overcome the GH-mediated resistant phenotype via modulating cell survival, death-related signaling routes and activating PA catabolic pathway.

Keywords

Breast cancer Growth hormone Curcumin NF-κB Apoptosis Polyamine 

Notes

Acknowledgements

The authors wish to thank Furkan Kaysın and Derya Bulut for their technical support.

Funding

This work was supported by the TUBITAK Scientific Projects Support Center (TUBITAK-1001 Program; Grant Number: 113Z791, 2014-2017).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

This article does not involve any studies with animals performed by any of the authors. The research has been performed on commercially available cell lines. Ethical approval for GH cloning experiment was obtained from the Marmara University Medical Faculty and Research Ethics Committee.

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Ajda Coker-Gurkan
    • 1
  • Merve Celik
    • 1
  • Merve Ugur
    • 1
  • Elif-Damla Arisan
    • 1
  • Pinar Obakan-Yerlikaya
    • 1
  • Zeynep Begum Durdu
    • 1
  • Narcin Palavan-Unsal
    • 1
  1. 1.Department of Molecular Biology and Genetics, Science and Literature FacultyIstanbul Kultur UniversityIstanbulTurkey

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