Dehydrocostus lactone suppresses cell growth and induces apoptosis in recombinant human papilloma virus‑18 HaCaT cells via the PI3K/Akt signaling pathway

Mol Med Rep. 2018 Jun;17(6):7925-7930. doi: 10.3892/mmr.2018.8805. Epub 2018 Mar 28.

Abstract

Dehydrocostus lactone is considered to be the major cholagogic ingredient of the Costus genus of plants. It exhibits strong cholagogic effects, and also exerts antimicrobial and antineoplastic activity. The present study aimed to investigate the effects of dehydrocostus lactone on the cell growth and apoptosis of recombinant human papilloma virus (HPV)‑18 HaCaT cells. The HPV‑18 genome was transfected into HaCaT cells, which were subsequently used for analysis. The results demonstrated that dehydrocostus lactone reduced the cell proliferation and induced apoptosis of HPV‑18 HaCaT cells, as determined by MTT and N‑acetyl‑Asp‑Glu‑Val‑Asp p‑nitroanilide assays, respectively. Furthermore, caspase‑3/9 activity was determined using a caspase‑3/9 activity kit and western blotting was performed to investigate the expression of certain proteins. The results demonstrated that caspase‑3/9 activities, and the protein expression of Bcl‑2‑associated X and p53, in HPV‑18 HaCaT cells were significantly increased, while cyclin D1 protein expression was suppressed by dehydrocostus lactone. Additionally, dehydrocostus lactone significantly upregulated the protein expression of phosphatase and tensin homolog and inhibited the phosphatidylinositol 3‑kinase (PI3K)/Akt signaling pathway in HPV‑18 HaCaT cells. Therefore, the results of the present study indicate that dehydrocostus lactone may suppress cell growth and induce apoptosis in recombinant HPV‑18 HaCaT cells via the PI3K/Akt signaling pathway, and may be a represent a novel potential therapeutic agent for the treatment of condyloma acuminatum.

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Female
  • Human papillomavirus 18
  • Humans
  • Lactones / chemistry
  • Lactones / pharmacology*
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / virology
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / drug effects*
  • Uterine Cervical Neoplasms / etiology
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Lactones
  • Sesquiterpenes
  • dehydrocostus lactone
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • Caspase 3
  • Caspase 9