Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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
_version_ 1783735833601245184
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
work_keys_str_mv AT yangyuchensh effectofestrogenonheteronemininducedantiproliferativeeffectinbreastcancercellswithdifferentestrogenreceptorstatus
AT lizilin effectofestrogenonheteronemininducedantiproliferativeeffectinbreastcancercellswithdifferentestrogenreceptorstatus
AT huangtungyung effectofestrogenonheteronemininducedantiproliferativeeffectinbreastcancercellswithdifferentestrogenreceptorstatus
AT sukuanwei effectofestrogenonheteronemininducedantiproliferativeeffectinbreastcancercellswithdifferentestrogenreceptorstatus
AT linchiyu effectofestrogenonheteronemininducedantiproliferativeeffectinbreastcancercellswithdifferentestrogenreceptorstatus
AT huangchihung effectofestrogenonheteronemininducedantiproliferativeeffectinbreastcancercellswithdifferentestrogenreceptorstatus
AT chenhanyu effectofestrogenonheteronemininducedantiproliferativeeffectinbreastcancercellswithdifferentestrogenreceptorstatus
AT lumeichin effectofestrogenonheteronemininducedantiproliferativeeffectinbreastcancercellswithdifferentestrogenreceptorstatus
AT huanghawming effectofestrogenonheteronemininducedantiproliferativeeffectinbreastcancercellswithdifferentestrogenreceptorstatus
AT leeshengyang effectofestrogenonheteronemininducedantiproliferativeeffectinbreastcancercellswithdifferentestrogenreceptorstatus
AT whangpengjaqueline effectofestrogenonheteronemininducedantiproliferativeeffectinbreastcancercellswithdifferentestrogenreceptorstatus
AT linhungyun effectofestrogenonheteronemininducedantiproliferativeeffectinbreastcancercellswithdifferentestrogenreceptorstatus
AT davispaulj effectofestrogenonheteronemininducedantiproliferativeeffectinbreastcancercellswithdifferentestrogenreceptorstatus
AT wangkuan effectofestrogenonheteronemininducedantiproliferativeeffectinbreastcancercellswithdifferentestrogenreceptorstatus