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

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...

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Autores principales: Kuo, Tian-Ni, Lin, Chun-Shiang, Li, Guan-De, Kuo, Cheng-Yi, Kao, Shao-Hsuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484641/
https://www.ncbi.nlm.nih.gov/pubmed/32922194
http://dx.doi.org/10.7150/ijms.48955
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author Kuo, Tian-Ni
Lin, Chun-Shiang
Li, Guan-De
Kuo, Cheng-Yi
Kao, Shao-Hsuan
author_facet Kuo, Tian-Ni
Lin, Chun-Shiang
Li, Guan-De
Kuo, Cheng-Yi
Kao, Shao-Hsuan
author_sort Kuo, Tian-Ni
collection PubMed
description 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.
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spelling pubmed-74846412020-09-12 Sesamin inhibits cervical cancer cell proliferation by promoting p53/PTEN-mediated apoptosis Kuo, Tian-Ni Lin, Chun-Shiang Li, Guan-De Kuo, Cheng-Yi Kao, Shao-Hsuan Int J Med Sci Research Paper 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. Ivyspring International Publisher 2020-08-25 /pmc/articles/PMC7484641/ /pubmed/32922194 http://dx.doi.org/10.7150/ijms.48955 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Kuo, Tian-Ni
Lin, Chun-Shiang
Li, Guan-De
Kuo, Cheng-Yi
Kao, Shao-Hsuan
Sesamin inhibits cervical cancer cell proliferation by promoting p53/PTEN-mediated apoptosis
title Sesamin inhibits cervical cancer cell proliferation by promoting p53/PTEN-mediated apoptosis
title_full Sesamin inhibits cervical cancer cell proliferation by promoting p53/PTEN-mediated apoptosis
title_fullStr Sesamin inhibits cervical cancer cell proliferation by promoting p53/PTEN-mediated apoptosis
title_full_unstemmed Sesamin inhibits cervical cancer cell proliferation by promoting p53/PTEN-mediated apoptosis
title_short Sesamin inhibits cervical cancer cell proliferation by promoting p53/PTEN-mediated apoptosis
title_sort sesamin inhibits cervical cancer cell proliferation by promoting p53/pten-mediated apoptosis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484641/
https://www.ncbi.nlm.nih.gov/pubmed/32922194
http://dx.doi.org/10.7150/ijms.48955
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