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Effect of Estrogen on Heteronemin-Induced Anti-proliferative Effect in Breast Cancer Cells With Different Estrogen Receptor Status
Estrogen (E(2)) has multiple functions in breast cancers including stimulating cancer growth and interfering with chemotherapeutic efficacy. Heteronemin, a marine sesterterpenoid-type natural product, has cytotoxicity on cancer cells. Breast cancer cell lines, MCF-7 and MDA-MB-231, were used for inv...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350732/ https://www.ncbi.nlm.nih.gov/pubmed/34381775 http://dx.doi.org/10.3389/fcell.2021.688607 |
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author | Yang, Yu-Chen S. H. Li, Zi-Lin Huang, Tung-Yung Su, Kuan-Wei Lin, Chi-Yu Huang, Chi-Hung Chen, Han-Yu Lu, Mei-Chin Huang, Haw-Ming Lee, Sheng-Yang Whang-Peng, Jaqueline Lin, Hung-Yun Davis, Paul J. Wang, Kuan |
author_facet | Yang, Yu-Chen S. H. Li, Zi-Lin Huang, Tung-Yung Su, Kuan-Wei Lin, Chi-Yu Huang, Chi-Hung Chen, Han-Yu Lu, Mei-Chin Huang, Haw-Ming Lee, Sheng-Yang Whang-Peng, Jaqueline Lin, Hung-Yun Davis, Paul J. Wang, Kuan |
author_sort | Yang, Yu-Chen S. H. |
collection | PubMed |
description | Estrogen (E(2)) has multiple functions in breast cancers including stimulating cancer growth and interfering with chemotherapeutic efficacy. Heteronemin, a marine sesterterpenoid-type natural product, has cytotoxicity on cancer cells. Breast cancer cell lines, MCF-7 and MDA-MB-231, were used for investigating mechanisms involved in inhibitory effect of E(2) on heteronemin-induced anti-proliferation in breast cancer cells with different estrogen receptor (ER) status. Cytotoxicity was detected by cell proliferation assay and flow cytometry, gene expressions were determined by qPCR, mechanisms were investigated by Western blot and Mitochondrial ROS assay. Heteronemin exhibited potent cytotoxic effects against both ER-positive and ER-negative breast cancer cells. E(2) stimulated cell growth in ER-positive breast cancer cells. Heteronemin induced anti-proliferation via suppressing activation of ERK1/2 and STAT3. Heteronemin suppressed E(2)-induced proliferation in both breast cancer cells although some gene expressions and anti-proliferative effects were inhibited in the presence of E(2) in MCF-7 and MDA-MB-231 cells with a higher concentration of heteronemin. Heteromenin decreased the Bcl-2/Bax ratio to inhibit proliferation in MDA-MB-231 but not in MCF-7 cells. Both heteronemin and E(2) increased mitochondrial reactive oxygen species but combined treatment reversed superoxide dismutase (SOD)s accumulation in MCF-7 cells. Heteronemin caused G(0)/G(1) phase arrest and reduced the percentage of cells in the S phase to suppress cancer cell growth. In conclusion, Heteronemin suppressed both ER-positive and ER-negative breast cancer cell proliferation. Interactions between E(2) and heteronemin in signal transduction, gene expressions, and biological activities provide insights into the complex pathways by which anti-proliferation is induced by heteronemin in E(2)-replete environments. |
format | Online Article Text |
id | pubmed-8350732 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83507322021-08-10 Effect of Estrogen on Heteronemin-Induced Anti-proliferative Effect in Breast Cancer Cells With Different Estrogen Receptor Status Yang, Yu-Chen S. H. Li, Zi-Lin Huang, Tung-Yung Su, Kuan-Wei Lin, Chi-Yu Huang, Chi-Hung Chen, Han-Yu Lu, Mei-Chin Huang, Haw-Ming Lee, Sheng-Yang Whang-Peng, Jaqueline Lin, Hung-Yun Davis, Paul J. Wang, Kuan Front Cell Dev Biol Cell and Developmental Biology Estrogen (E(2)) has multiple functions in breast cancers including stimulating cancer growth and interfering with chemotherapeutic efficacy. Heteronemin, a marine sesterterpenoid-type natural product, has cytotoxicity on cancer cells. Breast cancer cell lines, MCF-7 and MDA-MB-231, were used for investigating mechanisms involved in inhibitory effect of E(2) on heteronemin-induced anti-proliferation in breast cancer cells with different estrogen receptor (ER) status. Cytotoxicity was detected by cell proliferation assay and flow cytometry, gene expressions were determined by qPCR, mechanisms were investigated by Western blot and Mitochondrial ROS assay. Heteronemin exhibited potent cytotoxic effects against both ER-positive and ER-negative breast cancer cells. E(2) stimulated cell growth in ER-positive breast cancer cells. Heteronemin induced anti-proliferation via suppressing activation of ERK1/2 and STAT3. Heteronemin suppressed E(2)-induced proliferation in both breast cancer cells although some gene expressions and anti-proliferative effects were inhibited in the presence of E(2) in MCF-7 and MDA-MB-231 cells with a higher concentration of heteronemin. Heteromenin decreased the Bcl-2/Bax ratio to inhibit proliferation in MDA-MB-231 but not in MCF-7 cells. Both heteronemin and E(2) increased mitochondrial reactive oxygen species but combined treatment reversed superoxide dismutase (SOD)s accumulation in MCF-7 cells. Heteronemin caused G(0)/G(1) phase arrest and reduced the percentage of cells in the S phase to suppress cancer cell growth. In conclusion, Heteronemin suppressed both ER-positive and ER-negative breast cancer cell proliferation. Interactions between E(2) and heteronemin in signal transduction, gene expressions, and biological activities provide insights into the complex pathways by which anti-proliferation is induced by heteronemin in E(2)-replete environments. Frontiers Media S.A. 2021-07-26 /pmc/articles/PMC8350732/ /pubmed/34381775 http://dx.doi.org/10.3389/fcell.2021.688607 Text en Copyright © 2021 Yang, Li, Huang, Su, Lin, Huang, Chen, Lu, Huang, Lee, Whang-Peng, Lin, Davis and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Yang, Yu-Chen S. H. Li, Zi-Lin Huang, Tung-Yung Su, Kuan-Wei Lin, Chi-Yu Huang, Chi-Hung Chen, Han-Yu Lu, Mei-Chin Huang, Haw-Ming Lee, Sheng-Yang Whang-Peng, Jaqueline Lin, Hung-Yun Davis, Paul J. Wang, Kuan Effect of Estrogen on Heteronemin-Induced Anti-proliferative Effect in Breast Cancer Cells With Different Estrogen Receptor Status |
title | Effect of Estrogen on Heteronemin-Induced Anti-proliferative Effect in Breast Cancer Cells With Different Estrogen Receptor Status |
title_full | Effect of Estrogen on Heteronemin-Induced Anti-proliferative Effect in Breast Cancer Cells With Different Estrogen Receptor Status |
title_fullStr | Effect of Estrogen on Heteronemin-Induced Anti-proliferative Effect in Breast Cancer Cells With Different Estrogen Receptor Status |
title_full_unstemmed | Effect of Estrogen on Heteronemin-Induced Anti-proliferative Effect in Breast Cancer Cells With Different Estrogen Receptor Status |
title_short | Effect of Estrogen on Heteronemin-Induced Anti-proliferative Effect in Breast Cancer Cells With Different Estrogen Receptor Status |
title_sort | effect of estrogen on heteronemin-induced anti-proliferative effect in breast cancer cells with different estrogen receptor status |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350732/ https://www.ncbi.nlm.nih.gov/pubmed/34381775 http://dx.doi.org/10.3389/fcell.2021.688607 |
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