Quantum dot nanoprobe-based high-content monitoring of notch pathway inhibition of breast cancer stem cell by capsaicin

Mol Cell Probes. 2015 Dec;29(6):376-381. doi: 10.1016/j.mcp.2015.09.004. Epub 2015 Sep 15.

Abstract

Breast cancer is the major cause of cancer death for women worldwide. Breast cancer patients are treated with chemotherapy and radiotherapy. Although chemotherapy and radiotherapy are applied, some cancer cells still survive. These cells, called cancer stem cell (CSC), exhibit special capabilities, such as drug and radio resistance. The remaining CSC can trigger cancer recurrence. Thus, it is critical to find an effective way to target CSC. Capsaicin has been reported to affect anticancer activity in many cancers. It also has been shown that capsaicin induces apoptosis in the MCF-7 breast cancer cell line. In this study, we demonstrate that capsaicin causes dose-dependent growth disruption in breast CSC and inhibits translocation of notch intracellular membrane domain (NICD) into the nucleus. MCF-7 cells were treated with capsaicin at various concentrations (5 μM, 10 μM, and 20 μM) for 24 h. After capsaicin treatment, it was found that the number of breast CSC (%) decreased as the treatment concentration of capsaicin increased. This result was also confirmed with FACS. NICD translocation to the nucleus and apoptotic cell death of breast CSC were concurrently observed at the single breast CSC level using highly sensitive quantum dot (Qdot)-antibody nanoprobes. The control breast CSCs without the capsaicin treatment were able to translocate NICD into the nucleus. On the other hand, translocation of NICD into the nucleus was not observed in capsaicin-treated cells. In addition, apoptotic cell death was caused when the breast CSC were treated with capsaicin at more than 10 μM. Although many studies have shown that capsaicin produces anticancer activity in cancer cell lines, the present result is the first report to demonstrate that capsaicin is capable of causing breast CSC apoptotic cell death via inhibiting its notch signaling pathway.

Keywords: Breast cancer stem cell; Capsaicin; High-content assay; Notch; Quantum dot.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Capsaicin / pharmacology*
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • MCF-7 Cells
  • Nanoparticles
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Quantum Dots / metabolism*
  • Receptors, Notch / metabolism*
  • Signal Transduction / drug effects
  • Single-Cell Analysis / methods*

Substances

  • Receptors, Notch
  • Capsaicin