Asparanin A from Asparagus officinalis L. Induces G0/G1 Cell Cycle Arrest and Apoptosis in Human Endometrial Carcinoma Ishikawa Cells via Mitochondrial and PI3K/AKT Signaling Pathways

J Agric Food Chem. 2020 Jan 8;68(1):213-224. doi: 10.1021/acs.jafc.9b07103. Epub 2019 Dec 27.

Abstract

Asparanin A (AA), a steroidal saponin from Asparagus officinalis L., has anticancer activity: however, its detailed molecular mechanisms in endometrial cancer (EC) have not been studied so far. We evaluated the anticancer activity and underlying mechanism of AA on EC cell line Ishikawa in vitro and in vivo. AA inhibited the Ishikawa cell proliferation and caused cell morphology alteration and cell cycle arrest in G0/G1 phase. Moreover, it could induce apoptosis through mitochondrial pathway, including the deregulation of Bak/Bcl-xl ratio which led to the generation of ROS, up-regulation of cytochrome c followed by decrease of Δψm, and activation of caspases, besides inhibition of the PI3K/AKT/mTOR pathway. In vivo data showed that administration of AA significantly inhibited the tumor tissue cell proliferation, reduced the tumor growth, and induced the apoptosis occurrence. AA can be a possible functional food ingredient to cure endometrial cancer followed by clinical trials.

Keywords: Ishikawa cell; PI3K/AKT; asparagus; asparanin A; mitochondrial pathway.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Apoptosis / drug effects
  • Asparagus Plant / chemistry*
  • Cell Proliferation / drug effects
  • Cytochromes c / metabolism
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / physiopathology
  • Female
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • Humans
  • Mice, Inbred BALB C
  • Mitochondria / drug effects
  • Mitochondria / genetics
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Plant Extracts / administration & dosage*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Resting Phase, Cell Cycle / drug effects
  • Saponins / administration & dosage*
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • Saponins
  • asparanin A
  • Cytochromes c
  • Proto-Oncogene Proteins c-akt