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Glucose deprivation promotes apoptotic response to S1 by enhancing autophagy in human cervical cancer cells
BACKGROUND: S1 is a novel BH3 mimetic that can induce death in some types of cancer cells, such as melanoma B16, ovarian cancer SKOV3, and U251 glioma cells. S1 inhibits Bcl-2 and Mcl-1 expression and induces cancer cell apoptosis. Cancer cell survival is highly dependent on glucose. Here, we observ...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260140/ https://www.ncbi.nlm.nih.gov/pubmed/30538566 http://dx.doi.org/10.2147/CMAR.S184180 |
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author | Zhou, Li Kong, Qinghuan Zhang, Yunhan Yang, Wei Yan, Shan Li, Meihui Wang, Yidan Zhou, Yanjie Yu, Huimei Han, Liying |
author_facet | Zhou, Li Kong, Qinghuan Zhang, Yunhan Yang, Wei Yan, Shan Li, Meihui Wang, Yidan Zhou, Yanjie Yu, Huimei Han, Liying |
author_sort | Zhou, Li |
collection | PubMed |
description | BACKGROUND: S1 is a novel BH3 mimetic that can induce death in some types of cancer cells, such as melanoma B16, ovarian cancer SKOV3, and U251 glioma cells. S1 inhibits Bcl-2 and Mcl-1 expression and induces cancer cell apoptosis. Cancer cell survival is highly dependent on glucose. Here, we observed the effect of glucose deprivation on the apoptotic response to S1 in human cervical cancer (HeLa) cells. MATERIALS AND METHODS: Earle’s balanced salt solution (EBSS) was used to simulate glucose deprivation. MTT assay was used to analyze the cell survival rate, and Hoechst 33342 dye was used to detect the apoptosis in HeLa cells. Western blotting was used to detect the expression of ER stress and autophagy relative proteins. In addition, lysosomes were observed with Lyso-Tracker staining by confocal microscopy. RESULTS: S1 decreased cell distribution density and survival rate, and MTT assay showed that EBSS enhanced the inhibitory effects of S1 on HeLa cell growth. Hoechst 33342 dye showed that S1 led to pyknosis, fragmentation, and strong staining in HeLa cell nuclei, and EBSS enhanced these effects. Western blotting indicated that EBSS enhanced the expression of apoptosis-related proteins (cytochrome C, caspase-3, and poly[ADP-ribose] polymerase 1) induced by S1 in HeLa cells. S1 decreased p62 expression and increased the autophagosome-associated protein LC3-II expression, which indicated that S1 induced autophagy in HeLa cells. EBSS enhanced S1-induced autophagy in HeLa cells. Furthermore, autophagy inhibitor chloroquine enhanced S1-induced apoptosis in HeLa cells. CONCLUSION: These results indicate that EBSS exacerbates S1-induced autophagy and severe autophagy induced by EBSS and S1 could lead to apoptosis in HeLa cells. The results also suggest that EBSS enhances the sensitivity of HeLa cells to S1-induced apoptosis and that autophagy plays an important role in this process. |
format | Online Article Text |
id | pubmed-6260140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-62601402018-12-11 Glucose deprivation promotes apoptotic response to S1 by enhancing autophagy in human cervical cancer cells Zhou, Li Kong, Qinghuan Zhang, Yunhan Yang, Wei Yan, Shan Li, Meihui Wang, Yidan Zhou, Yanjie Yu, Huimei Han, Liying Cancer Manag Res Original Research BACKGROUND: S1 is a novel BH3 mimetic that can induce death in some types of cancer cells, such as melanoma B16, ovarian cancer SKOV3, and U251 glioma cells. S1 inhibits Bcl-2 and Mcl-1 expression and induces cancer cell apoptosis. Cancer cell survival is highly dependent on glucose. Here, we observed the effect of glucose deprivation on the apoptotic response to S1 in human cervical cancer (HeLa) cells. MATERIALS AND METHODS: Earle’s balanced salt solution (EBSS) was used to simulate glucose deprivation. MTT assay was used to analyze the cell survival rate, and Hoechst 33342 dye was used to detect the apoptosis in HeLa cells. Western blotting was used to detect the expression of ER stress and autophagy relative proteins. In addition, lysosomes were observed with Lyso-Tracker staining by confocal microscopy. RESULTS: S1 decreased cell distribution density and survival rate, and MTT assay showed that EBSS enhanced the inhibitory effects of S1 on HeLa cell growth. Hoechst 33342 dye showed that S1 led to pyknosis, fragmentation, and strong staining in HeLa cell nuclei, and EBSS enhanced these effects. Western blotting indicated that EBSS enhanced the expression of apoptosis-related proteins (cytochrome C, caspase-3, and poly[ADP-ribose] polymerase 1) induced by S1 in HeLa cells. S1 decreased p62 expression and increased the autophagosome-associated protein LC3-II expression, which indicated that S1 induced autophagy in HeLa cells. EBSS enhanced S1-induced autophagy in HeLa cells. Furthermore, autophagy inhibitor chloroquine enhanced S1-induced apoptosis in HeLa cells. CONCLUSION: These results indicate that EBSS exacerbates S1-induced autophagy and severe autophagy induced by EBSS and S1 could lead to apoptosis in HeLa cells. The results also suggest that EBSS enhances the sensitivity of HeLa cells to S1-induced apoptosis and that autophagy plays an important role in this process. Dove Medical Press 2018-11-23 /pmc/articles/PMC6260140/ /pubmed/30538566 http://dx.doi.org/10.2147/CMAR.S184180 Text en © 2018 Zhou et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Zhou, Li Kong, Qinghuan Zhang, Yunhan Yang, Wei Yan, Shan Li, Meihui Wang, Yidan Zhou, Yanjie Yu, Huimei Han, Liying Glucose deprivation promotes apoptotic response to S1 by enhancing autophagy in human cervical cancer cells |
title | Glucose deprivation promotes apoptotic response to S1 by enhancing autophagy in human cervical cancer cells |
title_full | Glucose deprivation promotes apoptotic response to S1 by enhancing autophagy in human cervical cancer cells |
title_fullStr | Glucose deprivation promotes apoptotic response to S1 by enhancing autophagy in human cervical cancer cells |
title_full_unstemmed | Glucose deprivation promotes apoptotic response to S1 by enhancing autophagy in human cervical cancer cells |
title_short | Glucose deprivation promotes apoptotic response to S1 by enhancing autophagy in human cervical cancer cells |
title_sort | glucose deprivation promotes apoptotic response to s1 by enhancing autophagy in human cervical cancer cells |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260140/ https://www.ncbi.nlm.nih.gov/pubmed/30538566 http://dx.doi.org/10.2147/CMAR.S184180 |
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