Dihydrotanshinone I inhibits ovarian cancer cell proliferation and migration by transcriptional repression of PIK3CA gene

J Cell Mol Med. 2020 Oct;24(19):11177-11187. doi: 10.1111/jcmm.15660. Epub 2020 Aug 29.

Abstract

Dihydrotanshinone I (DHTS), extracted from Salvia miltiorrhiza, was found to be the most effective compound of tanshen extracts against cancer cells in our previous studies. However, the therapeutic benefits and underlying mechanisms of DHTS on ovarian cancer remain uncertain. In this study, we demonstrated the cytocidal effects of DHTS on chemosensitive ovarian cancer cells with or without platinum-based chemotherapy. DHTS was able to inhibit proliferation and migration of ovarian cancer cells in vitro and in vivo through modulation of the PI3K/AKT signalling pathways. Combinatorial treatment of DHTS and cisplatin exhibited enhanced DNA damage in ovarian cancer cells. Overall, these findings suggest that DHTS induces ovarian cancer cells death via induction of DNA damage and inhibits ovarian cancer cell proliferation and migration.

Keywords: PIK3CA; dihydrotanshinone I; migration; ovarian cancer; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Ovarian Epithelial / enzymology
  • Carcinoma, Ovarian Epithelial / genetics
  • Carcinoma, Ovarian Epithelial / pathology
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Cell Movement* / genetics
  • Cell Proliferation / drug effects
  • Class I Phosphatidylinositol 3-Kinases / genetics*
  • Class I Phosphatidylinositol 3-Kinases / metabolism
  • Disease Models, Animal
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Furans / chemistry
  • Furans / pharmacology*
  • Furans / therapeutic use
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology*
  • Phenanthrenes / chemistry
  • Phenanthrenes / pharmacology*
  • Phenanthrenes / therapeutic use
  • Phosphatidylinositol 3-Kinases / metabolism
  • Platinum / pharmacology
  • Platinum / therapeutic use
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quinones / chemistry
  • Quinones / pharmacology*
  • Quinones / therapeutic use
  • Signal Transduction / drug effects
  • Transcription, Genetic* / drug effects
  • Zebrafish

Substances

  • Furans
  • Phenanthrenes
  • Quinones
  • Platinum
  • dihydrotanshinone I
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Proto-Oncogene Proteins c-akt