Oroxylin A exerts anticancer effects on human ovarian cancer cells via the PPARγ‑dependent reversal of the progesterone receptor membrane component 1/2 expression profile

Oncol Rep. 2020 Apr;43(4):1309-1318. doi: 10.3892/or.2020.7509. Epub 2020 Feb 21.

Abstract

Ovarian cancer is the most lethal gynecological cancer worldwide. To date, the therapeutic approaches available for the treatment of ovarian cancer are still very limited. The present study first demonstrated that the Chinese herb, Oroxylin A, exerts inhibitory effects on both the migratory ability and viability of ovarian cancer cells. Notably, the inhibitory effects of the drug occurred in a dose‑dependent manner. Oroxylin A only inhibited cell migration at the lower dose, whereas it induced early or late apoptosis at the middle or higher doses, respectively. Mechanistically, Oroxylin A increased peroxisome proliferator‑activated receptor gamma (PPARγ) expression and altered the expression profile of progesterone receptor membrane component (PGRMC)1/2. Notably, PPARγ was revealed to play a central role in Oroxylin A‑mediated anticancer activity. The silencing of PPARγ significantly abrogated Oroxylin A‑induced apoptotic cell death and restored the expression profile of the PGRMC1/2 family in ovarian cancer cells. Collectively, the present study revealed that Oroxylin A exerted marked anticancer effects against ovarian cancer in vitro. Thus, Oroxylin A may have potential for use as a complementary therapy in the treatment of ovarian cancer.

Keywords: Oroxylin A; ovarian cancer; apoptosis; signaling pathway.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Flavonoids / pharmacology*
  • Humans
  • Membrane Proteins / metabolism*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • PPAR gamma / agonists*
  • Receptors, Progesterone / metabolism*
  • Signal Transduction

Substances

  • Flavonoids
  • Membrane Proteins
  • PGRMC1 protein, human
  • PGRMC2 protein, human
  • PPAR gamma
  • PPARG protein, human
  • Receptors, Progesterone
  • 5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one