Simplified Theta-defensin [Ser3,7,12,16] RTD-2 Analog Is Involved in Proteasomal Degradation Pathway in Breast Cancer

Anticancer Res. 2021 Nov;41(11):5415-5423. doi: 10.21873/anticanres.15353.

Abstract

Background/aim: Antimicrobial peptides are part of the innate immune response, regulate inflammation and initiate acquired immunity. This study focused on theta-defensins that have been shown to have anticancer properties.

Materials and methods: RTD-2 analogs were synthesized on a peptide synthesizer. Cell viability was estimated using the MTT test. Immunoprecipitation assay was conducted to determine the molecular partner of the [Ser3,7,12,16]-RTD-2 analog.

Results: Here, we present the biologically active [Ser3,7,12,16]-RTD-2 analog that selectively targets various types of breast cancer cells. Immunoprecipitation protein-protein interaction studies showed eleven proteins common to MDA-MB-231 and T47D cell lines. Taking into account their cellular location, it can be concluded that the synthesized peptide interacts mainly with nuclear proteins, which correlates with the obtained microscopic image.

Conclusion: Proteins that interact strongly with the [Ser3,7,12,16]-RTD-2 analog are closely related to the proteasomal protein degradation pathway. As the activity of the ubiquitin-proteasome system is markedly increased in patients with breast cancer, it is likely that selective modulation of this system may be a useful method for breast cancer treatment.

Keywords: Theta-defensins; breast cancer; cell culture; immunoprecipitation.

MeSH terms

  • Amino Acid Sequence
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Defensins / chemistry
  • Defensins / pharmacology*
  • Drug Design*
  • Female
  • Humans
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology*
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteolysis
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Defensins
  • Peptides, Cyclic
  • rhesus theta defensin-2
  • theta-defensin
  • Proteasome Endopeptidase Complex