Luteoloside Inhibits Proliferation and Promotes Intrinsic and Extrinsic Pathway-Mediated Apoptosis Involving MAPK and mTOR Signaling Pathways in Human Cervical Cancer Cells

Int J Mol Sci. 2018 Jun 5;19(6):1664. doi: 10.3390/ijms19061664.


Cervical cancer is a common gynecological malignancy with high incidence and mortality. Drugs commonly used in chemotherapy are often accompanied by strong side-effects. To find an anti-cervical cancer drug with high effects and low toxicity, luteoloside was used to treat the cervical cancer cell line Hela to investigate its effects on cell morphology, proliferation, apoptosis, and related proteins. The study demonstrated that luteoloside could inhibit proliferation remarkably; promote apoptosis and cytochrome C release; decrease the mitochondrial membrane potential and reactive oxygen species level; upregulate the expression of Fas, Bax, p53, phospho-p38, phospho-JNK, and cleaved PARP; downregulate the expression of Bcl-2 and phospho-mTOR; activate caspase-3 and caspase-8; change the nuclear morphology, and fragmentate DNA in Hela cells. These results strongly suggest that luteoloside can significantly inhibit the proliferation and trigger apoptosis in Hela cells. In contrast, luteoloside had less proliferation inhibiting effects on the normal cell lines HUVEC12 and LO2, and minor apoptosis promoting effects on HUVEC12 cells. Furthermore, the luteoloside-induced apoptosis in Hela cells is mediated by both intrinsic and extrinsic pathways and the effects of luteoloside may be regulated by the mitogen-activated protein kinases and mTOR signaling pathways via p53.

Keywords: MAPK; apoptosis; cervical cancer; luteoloside; mTOR; proliferation.

MeSH terms

  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects*
  • Female
  • Glucosides / administration & dosage*
  • HeLa Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Luteolin / administration & dosage*
  • MAP Kinase Kinase 1 / genetics
  • Membrane Potential, Mitochondrial / drug effects
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology


  • Glucosides
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • luteolin-7-glucoside
  • TOR Serine-Threonine Kinases
  • MAP Kinase Kinase 1
  • Luteolin