1. Sesamin inhibits cervical cancer cell proliferation by promoting p53/PTEN-mediated apoptosis.
- Author
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Kuo TN, Lin CS, Li GD, Kuo CY, and Kao SH
- Subjects
- Cell Cycle, Cell Proliferation drug effects, Dioxoles therapeutic use, Drug Screening Assays, Antitumor, Female, HeLa Cells, Humans, Lignans therapeutic use, PTEN Phosphohydrolase metabolism, Signal Transduction drug effects, Tumor Suppressor Protein p53 metabolism, Uterine Cervical Neoplasms pathology, Apoptosis drug effects, Dioxoles pharmacology, Lignans pharmacology, Uterine Cervical Neoplasms drug therapy
- Abstract
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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)
- Published
- 2020
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