Dihydromyricetin Induces Apoptosis and Reverses Drug Resistance in Ovarian Cancer Cells by p53-mediated Downregulation of Survivin

Sci Rep. 2017 Apr 24:7:46060. doi: 10.1038/srep46060.

Abstract

Ovarian cancer is one of the leading causes of death in gynecological malignancies, and the resistance to chemotherapeutic agents remains a major challenge to successful ovarian cancer chemotherapy. Dihydromyricetin (DHM), a natural flavonoid derived from Ampeopsis Grossdentata, has been widely applied in food industry and medicine for a long time. However, little is known about the effects of DHM on ovarian cancer and the underlying mechanisms. In this study, we demonstrated that DHM could effectively inhibit the proliferation of ovarian cancer cells and induce cell apoptosis. Survivin, an inhibitor of apoptosis (IAPs) family member, exhibited a decreased expression level after DHM treatment, which may be attributed to the activation of p53. Moreover, DHM markedly sensitized paclitaxel (PTX) and doxorubicin (DOX) resistant ovarian cancer cells to PTX and DOX by inhibiting survivin expression. Collectively, our findings highlight a previously undiscovered effect of DHM, which induces apoptosis and reverses multi-drug resistance against ovarian cancer cells through downregulation of survivin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Down-Regulation / drug effects*
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Flavonols / chemistry
  • Flavonols / pharmacology*
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*
  • Paclitaxel / pharmacology
  • S Phase / drug effects
  • Signal Transduction / drug effects
  • Survivin
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • BIRC5 protein, human
  • Flavonols
  • Inhibitor of Apoptosis Proteins
  • Survivin
  • Tumor Suppressor Protein p53
  • Doxorubicin
  • dihydromyricetin
  • Paclitaxel