Sesamin inhibits cervical cancer cell proliferation by promoting p53/PTEN-mediated apoptosis

Int J Med Sci. 2020 Aug 25;17(15):2292-2298. doi: 10.7150/ijms.48955. eCollection 2020.


Background: Sesamin is a major bioactive compound in sesame seeds and has various biological properties, including anti-inflammatory and anticancer activities. Here, we explored whether sesamin activates p53, which is widely inhibited in cervical cancer cells, thereby inducing p53-mediated apoptosis. Methods: Human HeLa and SiHa cervical cancer cells and normal Hs68 dermal cells were used as cell models. Cell proliferation, cell cycle distribution, and apoptosis were evaluated by the CCK-8 assay and flow cytometry using PI/Annexin V staining, respectively. Protein expression and phosphorylation were determined using western blotting. The involvement of p53 in the apoptotic cascade was assessed by a specific inhibitor. Results: Sesamin (75 and 150 μM) clearly inhibited SiHa and HeLa cell proliferation in a dose-dependent fashion, but did not affect the proliferation of Hs68 cells. Meanwhile, sesamin increased the sub-G1 phase ratio and apoptosis, up to approximately 38.5% and 37.8%, respectively. Furthermore, sesamin induced p53 phosphorylation at serine-46 and serine-15 and upregulated the levels of PUMA, Bax, and PTEN, while inhibiting AKT phosphorylation at serine-473. Inhibition of p53 by pifithrin-α significantly reduced the levels of PUMA, Bax, and PTEN but restored AKT phosphorylation in SiHa cells exposed to sesamin. Pifithrin-α also reduced apoptosis and restored the proliferation of HeLa and SiHa cells exposed to sesamin. Conclusions: These findings indicate that sesamin inhibits cervical cancer cell proliferation, and its mechanism may be attributed to the induction of p53/PTEN-mediated apoptosis. This suggests that sesamin might be useful as an adjuvant in promoting anti-cervical cancer treatments.

Keywords: Apoptosis.; Cervical cancer cell; PTEN; PUMA; Sesamin; p53.

MeSH terms

  • Apoptosis / drug effects*
  • Cell Cycle
  • Cell Proliferation / drug effects
  • Dioxoles / pharmacology*
  • Dioxoles / therapeutic use
  • Drug Screening Assays, Antitumor
  • Female
  • HeLa Cells
  • Humans
  • Lignans / pharmacology*
  • Lignans / therapeutic use
  • PTEN Phosphohydrolase / metabolism
  • Signal Transduction / drug effects
  • Tumor Suppressor Protein p53 / metabolism
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / pathology


  • Dioxoles
  • Lignans
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • sesamin