Curcumol Suppresses Triple-negative Breast Cancer Metastasis by Attenuating Anoikis Resistance via Inhibition of Skp2-mediated Transcriptional Addiction

Anticancer Res. 2020 Oct;40(10):5529-5538. doi: 10.21873/anticanres.14565.

Abstract

Background/aim: Triple-negative breast cancer (TNBC) is a unique subtype that lacks expression of several conventional biomarkers and has a higher incidence of lymph node invasion and distal metastasis among all breast cancers. Anoikis resistance is the fundamental reason behind tumor cells' survival without their attachment to the extracellular matrix and metastasis to distal organs. Therefore, finding novel anti-cancer drugs that can suppress anoikis resistance in cancer cells is critical for patients with TNBC.

Materials and methods: Curcumol, a natural compound, was used to assess whether it can inhibit the anoikis resistance and affects cell mortality and motility of IV2-1 TNBC cells.

Results: Curcumol suppressed anoikis resistance and inhibited TNBC cell survival in suspension. Additionally, these anti-cancer effects induced by curcumol could be related to the YAP1/Skp2 molecular pathway.

Conclusion: Curcumol is an effective Skp2-targeted therapy that attenuates anoikis resistance and metastasis in TNBC cells.

Keywords: Skp2; Triple-negative breast cancer; anoikis; curcumol.

MeSH terms

  • Anoikis / drug effects
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Metastasis
  • S-Phase Kinase-Associated Proteins / genetics*
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / drug effects
  • Transcription, Genetic / drug effects
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • MicroRNAs
  • S-Phase Kinase-Associated Proteins
  • Sesquiterpenes
  • curcumol