Anti-Proliferation Effect of Theasaponin E₁ on the ALDH-Positive Ovarian Cancer Stem-Like Cells

Molecules. 2018 Jun 17;23(6):1469. doi: 10.3390/molecules23061469.

Abstract

Ovarian cancer has the highest mortality rate of all gynecological malignancies and the five-year death rate of patients has remained high in the past five decades. Recently, with the rise of cancer stem cells (CSCs) theory, an increasing amount of research has suggested that CSCs give rise to tumor recurrence and metastasis. Theasaponin E₁ (TSE₁), which was isolated from green tea (Camellia sinensis) seeds, has been proposed to be an effective compound for tumor treatment. However, studies on whether TSE₁ takes effect through CSCs have rarely been reported. In this paper, ALDH-positive (ALDH+) ovarian cancer stem-like cells from two platinum-resistant ovarian cancer cell lines A2780/CP70 and OVCAR-3 were used to study the anti-proliferation effect of TSE₁ on CSCs. The ALDH+ cells showed significantly stronger sphere forming vitality and stronger cell migration capability. In addition, the stemness marker proteins CD44, Oct-4, Nanog, as well as Bcl-2 and MMP-9 expression levels of ALDH+ cells were upregulated compared with the original tumor cells, indicating that they have certain stem cell characteristics. At the same time, the results showed that TSE₁ could inhibit cell proliferation and suspension sphere formation in ALDH+ cells. Our data suggests that TSE₁ as a natural compound has the potential to reduce human ovarian cancer mortality. However, more research is still needed to find out the molecular mechanism of TSE₁-mediated inhibition of ALDH+ cells and possible drug applications on the disease.

Keywords: ALDH; Camellia sinensis; cancer stem cells; ovarian cancer; theasaponin E1.

MeSH terms

  • Aldehyde Dehydrogenase / metabolism*
  • Biomarkers / metabolism
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Molecular Structure
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / chemistry
  • Oleanolic Acid / pharmacology
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism*
  • Saponins / chemistry
  • Saponins / pharmacology*
  • Tea / chemistry

Substances

  • Biomarkers
  • Saponins
  • Tea
  • theasaponin E1
  • Oleanolic Acid
  • Aldehyde Dehydrogenase