Plantamajoside inhibits hypoxia-induced migration and invasion of human cervical cancer cells through the NF-κB and PI3K/akt pathways

J Recept Signal Transduct Res. 2021 Aug;41(4):339-348. doi: 10.1080/10799893.2020.1808679. Epub 2020 Aug 30.

Abstract

Plantamajoside (PMS) is a major compound of Plantago asiatica and possesses anti-tumor property in several types of cancers. However, the effect of PMS on cervical cancer has not been investigated. This study aimed to investigate the effect of PMS on the migration and invasion of cervical cancer cell lines under hypoxic condition. Our results demonstrated that PMS significantly inhibited hypoxia-caused increases in cell migration and invasion of cervical cancer cells. The hypoxia-induced epithelial-mesenchymal transition (EMT) process was prevented by PMS with increased E-cadherin expression, and decreased expression levels of N-cadherin and vimentin in cervical cancer cells. Besides, the expression levels of transcription factors slug and snail were suppressed by PMS in hypoxia-induced cervical cancer cells. The increased mRNA and protein levels of hypoxia-inducible factor 1alpha (HIF-1α) in hypoxia-induced cervical cancer cells were prevented by PMS. Furthermore, PMS blocked the hypoxia-induced activation of NF-κB and PI3K/Akt pathway in cervical cancer cells. Taken together, these findings suggest that PMS exerted an anti-tumor activity in cervical cancer through preventing the hypoxia-induced EMT. Thus, PMS might serve as a therapeutic agent for the treatment of cervical cancer.

Keywords: Cervical cancer; EMT; NF-κB; PI3K/Akt; hypoxia; plantamajoside.

MeSH terms

  • Cadherins / metabolism
  • Catechols / pharmacology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival
  • Epithelial-Mesenchymal Transition
  • Female
  • Glucosides / pharmacology*
  • Humans
  • Hypoxia
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • NF-kappa B / metabolism*
  • Neoplasm Invasiveness
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Small Interfering / metabolism
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / metabolism*
  • Vimentin / metabolism

Substances

  • Cadherins
  • Catechols
  • Glucosides
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • NF-kappa B
  • RNA, Small Interfering
  • Vimentin
  • plantamajoside
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt