Dioscorea deltoidea Leaf Extract (DDLE) Targets PI3K/AKT/mTOR Pathway and Inhibits Ovarian Cancer Cell Growth

Dokl Biochem Biophys. 2021 Mar;497(1):144-150. doi: 10.1134/S1607672921020058. Epub 2021 Apr 24.

Abstract

Ovarian cancer is the malignant tumour of the female reproductive organ with highest mortality rate among all the types of gynaecological tumours. This study investigated the effect of Dioscorea deltoidea leaf extract (DDLE) on OV-90 and CAOV4 ovarian cancer cells. The results demonstrated that DDLE suppresses OV-90 and CAOV3 cell viability significantly in dose dependent manner. The OV-90 and CAOV3 cell viability were reduced to 24 and 27% respectively with 20 mg/mL DDLE treatment. Five mg/mL DDLE treatment of OV-90 and CAOV4 cells raised percentage of cells in G2-phase to 55.9 and 51.2%, respectively. In 5 mg/mL DDLE -treated OV-90 and CAOV4 cells a prominent suppression in cyclin-D1 and cyclin B1 proteins was observed in 48 h. The DDLE treatment promoted OV-90 and CAOV3 cell apoptosis to 34.65 and 29.89%, respectively. The Fas, FasL, cleaved caspase-3, and Bax levels were up-regulated markedly in the cells after DDLE treatment. Moreover, DDLE treatment suppressed p-mTOR, p-AKT and p-PI3K expression in OV-90 and CAOV3 cells. Thus, DDLE suppressed ovary cancer cell viability and elevated cell apoptosis. Inhibitory effect of DDLE on ovarian cancer cells is associated with targeting PI3K/AKT/mTOR pathway.

Keywords: Dioscorea deltoidei; caspases; chemotherapeutic; gynaecological tumors; ovary cancer.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dioscorea / chemistry*
  • Female
  • Humans
  • Ovarian Neoplasms / pathology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism*
  • Up-Regulation / drug effects

Substances

  • Antineoplastic Agents
  • Plant Extracts
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases