Standardized Saponin Extract from Baiye No.1 Tea (Camellia sinensis) Flowers Induced S Phase Cell Cycle Arrest and Apoptosis via AKT-MDM2-p53 Signaling Pathway in Ovarian Cancer Cells

Molecules. 2020 Jul 31;25(15):3515. doi: 10.3390/molecules25153515.

Abstract

Ovarian cancer is considered to be one of the most serious malignant tumors in women. Natural compounds have been considered as important sources in the search for new anti-cancer agents. Saponins are characteristic components of tea (Camellia sinensis) flower and have various biological activities, including anti-tumor effects. In this study, a high purity standardized saponin extract, namely Baiye No.1 tea flower saponin (BTFS), which contained Floratheasaponin A and Floratheasaponin D, were isolated from tea (Camellia sinensis cv. Baiye 1) flowers by macroporous resin and preparative liquid chromatography. Then, the component and purity were detected by UPLC-Q-TOF/MS/MS. This high purity BTFS inhibited the proliferation of A2780/CP70 cancer cells dose-dependently, which is evidenced by the inhibition of cell viability, reduction of colony formation ability, and suppression of PCNA protein expression. Further research found BTFS induced S phase cell cycle arrest by up-regulating p21 proteins expression and down-regulating Cyclin A2, CDK2, and Cdc25A protein expression. Furthermore, BTFS caused DNA damage and activated the ATM-Chk2 signaling pathway to block cell cycle progression. Moreover, BTFS trigged both extrinsic and intrinsic apoptosis-BTFS up-regulated the expression of death receptor pathway-related proteins DR5, Fas, and FADD and increased the ratio of pro-apoptotic/anti-apoptotic proteins of the Bcl-2 family. BTFS-induced apoptosis seems to be related to the AKT-MDM2-p53 signaling pathway. In summary, our results demonstrate that BTFS has the potential to be used as a nutraceutical for the prevention and treatment of ovarian cancer.

Keywords: A2780/CP70 ovarian cancer cells; BTFS; S phase cell cycle arrest; apoptosis; tea (Camellia sinensis) flowers.

MeSH terms

  • Apoptosis / drug effects*
  • Camellia sinensis / chemistry*
  • Camellia sinensis / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclin A2 / genetics
  • Cyclin A2 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Female
  • Flowers / chemistry
  • Flowers / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Oleanolic Acid / analogs & derivatives
  • Oleanolic Acid / isolation & purification
  • Oleanolic Acid / pharmacology
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Plant Extracts / chemistry*
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • S Phase Cell Cycle Checkpoints / drug effects*
  • Saponins / chemistry
  • Saponins / isolation & purification
  • Saponins / pharmacology*
  • Signal Transduction / drug effects*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Cyclin A2
  • Plant Extracts
  • Proliferating Cell Nuclear Antigen
  • Saponins
  • Tumor Suppressor Protein p53
  • floratheasaponin A
  • Cyclin-Dependent Kinase Inhibitor p27
  • Oleanolic Acid
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Proto-Oncogene Proteins c-akt