Ribosomal protein S3 regulates XIAP expression independently of the NF-κB pathway in breast cancer cells

Oncol Rep. 2017 Nov;38(5):3205-3210. doi: 10.3892/or.2017.6008. Epub 2017 Sep 27.


The X-linked inhibitor of apoptosis (XIAP) confers the resistance of various types of cancer to standard chemotherapeutic agents such as anthracycline and taxane. In breast cancer, XIAP is known to be overexpressed. However, the mechanisms underlying the overexpression of XIAP remain currently unclear. In order to elucidate the mechanisms responsible for the overexpression of the XIAP protein in breast cancer, we attempted to clarify the mechanisms by which the natural compound curcumin downregulates XIAP in breast cancer cells. In that process, we identified the ribosomal protein S3 (RPS3) as a curcumin‑binding protein using curcumin-fixed magnetic FG beads. The knockdown of RPS3 inhibited cell growth and induced apoptosis as well as the downregulation of XIAP in breast cancer cells. Although RPS3 is known to directly bind to and activate the nuclear factor-κB (NF-κB), which induces several anti-apoptotic genes such as XIAP, the knockdown of RPS3 unexpectedly reduced the levels of the XIAP protein, but not the mRNA level of XIAP and the transcription factor NF-κB activity. These results reveal that RPS3 upregulates XIAP independently of the NF-κB pathway in human breast cancer cells.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carrier Proteins / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Curcumin / administration & dosage
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Humans
  • NF-kappa B / genetics
  • Ribosomal Proteins / antagonists & inhibitors
  • Ribosomal Proteins / genetics*
  • X-Linked Inhibitor of Apoptosis Protein / genetics*


  • Carrier Proteins
  • NF-kappa B
  • RPS3 protein, human
  • Ribosomal Proteins
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • Curcumin