Active cell death induced by the anti-estrogens tamoxifen and ICI 164 384 in human mammary carcinoma cells (MCF-7) in culture: the role of autophagy

Active cell death induced by the anti-estrogens tamoxifen and ICI 164 384 in human mammary... Active cell death in hormone-dependent cells was studied using cultured human mammary carcinoma cells (MCF-7) treated with the anti-estrogens (AEs) tamoxifen (TAM), 4-hydroxy-tamoxifen (OH-TAM) or ICI 164 384 (10 −8 –10 −5 M) as a model. The following results were obtained. (i) In untreated MCF-7 cells a wave of replication occurred in the first 5 days of culture. All three AEs caused a dose-dependent inhibition of cell replication. (ii) TAM and OH-TAM at 10 −5 M, but not ICI 164 384, caused lytic cell death (necrosis) within 24 h, which was not inhibited by estradiol (10 −9 –10 −6 M). (iii) Lower concentrations of TAM or OH-TAM (up to 10 −6 M) or ICI 164 384 induced a more gradual appearance of cell death beginning at day 3. This type of cell death was inhibited by estradiol (10 −9 M), indicating its active nature. (iv) Nuclei showed two distinct patterns of alternation: (a) apoptosis-like condensation and fragmentation of chromatin to crescent masses abutting the nuclear envelope; (b) condensation of the chromatin to a single, pyknotic mass in the center of the nucleus, detached from the nuclear envelope. Quantitative histological evaluation revealed the predominance of pyknosis. (v) Biochemical DNA analysis revealed that only a relatively small amount of the total DNA was finally degraded into low molecular weight fragments (20 kb and less). (vi) Active cell death, with both apoptotic and pyknotic nuclear morphology, was associated with extensive formation of autophagic vacuoles (AV). 3-Methyladenine, a known inhibitor of AV formation, partially prevented cell death as detected by nuclear changes. (vii) ICI 164 384 was about 10 times more effective than TAM or OH-TAM at inhibiting DNA synthesis, but had equal potency in inducing active cell death. It is concluded that AEs have anti-proliferative and anti-survival effects on MCF-7 human mammary cancer cells in culture. These two effects are under separate control because they differ by kinetics, dose dependence and sensitivity to the various AEs. Active cell death in MCF-7 cells seems to be initiated by autophagy, in contrast to concepts of apoptosis, and thus corresponds to autophagic/lysosomal or type II death as previously defined. This may be important because of biochemical and molecular differences between these various subtypes of active cell death. © Oxford University Press « Previous | Next Article » Table of Contents This Article Carcinogenesis (1996) 17 (8): 1595-1607. doi: 10.1093/carcin/17.8.1595 » Abstract Free Full Text (PDF) Free Classifications ORIGINAL ARTICLES: CANCER BIOLOGY Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Bursch, W. Articles by Hermann, R. S. Search for related content PubMed PubMed citation Articles by Bursch, W. Articles by Ellinger, A. Articles by Kienzl, H. Articles by Török, L. Articles by Pandey, S. Articles by Sikorska, M. Articles by Walker, R. Articles by Hermann, R. S. Related Content Load related web page information Share Email this article CiteULike Delicious Facebook Google+ Mendeley Twitter What's this? Search this journal: Advanced » Current Issue November 2015 36 (11) Alert me to new issues The Journal About this journal Rights & Permissions Dispatch date of the next issue This journal is a member of the Committee on Publication Ethics (COPE) We are mobile – find out more Journals Career Network Impact factor: 5.334 5-Yr impact factor: 5.698 Editor-in-Chief Dr Curtis C Harris, USA View full editorial board For Authors Instructions to authors Online submission Submit Now! Self archiving policy Open access options for authors - visit Oxford Open This journal enables compliance with the NIH Public Access Policy Alerting Services Email table of contents Email Advance Access CiteTrack XML RSS feed Corporate Services Advertising sales Reprints Supplements var taxonomies = ("MED00710"); Most Most Read Apoptosis in cancer Modulation of E-cadherin expression by K-Ras; involvement of DNA methyltransferase-3b Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead Tumor progression and metastasis Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability » View all Most Read articles Most Cited Oxyradicals and DNA damage Sensing and repairing DNA double-strand breaks Functional role of estrogen metabolism in target cells: review and perspectives Apoptosis in cancer Nucleotide excision repair and human syndromes » View all Most Cited articles Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department. Online ISSN 1460-2180 - Print ISSN 0143-3334 Copyright © 2015 Oxford University Press Oxford Journals Oxford University Press Site Map Privacy Policy Cookie Policy Legal Notices Frequently Asked Questions Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan Academic & Professional books Children's & Schools Books Dictionaries & Reference Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks International Education Unit Law Medicine Music Online Products & Publishing Oxford Bibliographies Online Oxford Dictionaries Online Oxford English Dictionary Oxford Language Dictionaries Online Oxford Scholarship Online Reference Rights and Permissions Resources for Retailers & Wholesalers Resources for the Healthcare Industry Very Short Introductions World's Classics function fnc_onDomLoaded() { var query_context = getQueryContext(); PF_initOIUnderbar(query_context,":QS:default","","JRN"); PF_insertOIUnderbar(0); }; if (window.addEventListener) { window.addEventListener('load', fnc_onDomLoaded, false); } else if (window.attachEvent) { window.attachEvent('onload', fnc_onDomLoaded); } var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); try { var pageTracker = _gat._getTracker("UA-189672-16"); pageTracker._setDomainName(".oxfordjournals.org"); pageTracker._trackPageview(); } catch(err) {} http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Carcinogenesis Oxford University Press

Active cell death induced by the anti-estrogens tamoxifen and ICI 164 384 in human mammary carcinoma cells (MCF-7) in culture: the role of autophagy

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Publisher
Oxford University Press
Copyright
Copyright © 2015 Oxford University Press
ISSN
0143-3334
eISSN
1460-2180
D.O.I.
10.1093/carcin/17.8.1595
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Abstract

Active cell death in hormone-dependent cells was studied using cultured human mammary carcinoma cells (MCF-7) treated with the anti-estrogens (AEs) tamoxifen (TAM), 4-hydroxy-tamoxifen (OH-TAM) or ICI 164 384 (10 −8 –10 −5 M) as a model. The following results were obtained. (i) In untreated MCF-7 cells a wave of replication occurred in the first 5 days of culture. All three AEs caused a dose-dependent inhibition of cell replication. (ii) TAM and OH-TAM at 10 −5 M, but not ICI 164 384, caused lytic cell death (necrosis) within 24 h, which was not inhibited by estradiol (10 −9 –10 −6 M). (iii) Lower concentrations of TAM or OH-TAM (up to 10 −6 M) or ICI 164 384 induced a more gradual appearance of cell death beginning at day 3. This type of cell death was inhibited by estradiol (10 −9 M), indicating its active nature. (iv) Nuclei showed two distinct patterns of alternation: (a) apoptosis-like condensation and fragmentation of chromatin to crescent masses abutting the nuclear envelope; (b) condensation of the chromatin to a single, pyknotic mass in the center of the nucleus, detached from the nuclear envelope. Quantitative histological evaluation revealed the predominance of pyknosis. (v) Biochemical DNA analysis revealed that only a relatively small amount of the total DNA was finally degraded into low molecular weight fragments (20 kb and less). (vi) Active cell death, with both apoptotic and pyknotic nuclear morphology, was associated with extensive formation of autophagic vacuoles (AV). 3-Methyladenine, a known inhibitor of AV formation, partially prevented cell death as detected by nuclear changes. (vii) ICI 164 384 was about 10 times more effective than TAM or OH-TAM at inhibiting DNA synthesis, but had equal potency in inducing active cell death. It is concluded that AEs have anti-proliferative and anti-survival effects on MCF-7 human mammary cancer cells in culture. These two effects are under separate control because they differ by kinetics, dose dependence and sensitivity to the various AEs. Active cell death in MCF-7 cells seems to be initiated by autophagy, in contrast to concepts of apoptosis, and thus corresponds to autophagic/lysosomal or type II death as previously defined. This may be important because of biochemical and molecular differences between these various subtypes of active cell death. © Oxford University Press « Previous | Next Article » Table of Contents This Article Carcinogenesis (1996) 17 (8): 1595-1607. doi: 10.1093/carcin/17.8.1595 » Abstract Free Full Text (PDF) Free Classifications ORIGINAL ARTICLES: CANCER BIOLOGY Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Bursch, W. Articles by Hermann, R. S. Search for related content PubMed PubMed citation Articles by Bursch, W. Articles by Ellinger, A. Articles by Kienzl, H. Articles by Török, L. Articles by Pandey, S. Articles by Sikorska, M. Articles by Walker, R. Articles by Hermann, R. S. Related Content Load related web page information Share Email this article CiteULike Delicious Facebook Google+ Mendeley Twitter What's this? Search this journal: Advanced » Current Issue November 2015 36 (11) Alert me to new issues The Journal About this journal Rights & Permissions Dispatch date of the next issue This journal is a member of the Committee on Publication Ethics (COPE) We are mobile – find out more Journals Career Network Impact factor: 5.334 5-Yr impact factor: 5.698 Editor-in-Chief Dr Curtis C Harris, USA View full editorial board For Authors Instructions to authors Online submission Submit Now! Self archiving policy Open access options for authors - visit Oxford Open This journal enables compliance with the NIH Public Access Policy Alerting Services Email table of contents Email Advance Access CiteTrack XML RSS feed Corporate Services Advertising sales Reprints Supplements var taxonomies = ("MED00710"); Most Most Read Apoptosis in cancer Modulation of E-cadherin expression by K-Ras; involvement of DNA methyltransferase-3b Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead Tumor progression and metastasis Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability » View all Most Read articles Most Cited Oxyradicals and DNA damage Sensing and repairing DNA double-strand breaks Functional role of estrogen metabolism in target cells: review and perspectives Apoptosis in cancer Nucleotide excision repair and human syndromes » View all Most Cited articles Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department. Online ISSN 1460-2180 - Print ISSN 0143-3334 Copyright © 2015 Oxford University Press Oxford Journals Oxford University Press Site Map Privacy Policy Cookie Policy Legal Notices Frequently Asked Questions Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan Academic & Professional books Children's & Schools Books Dictionaries & Reference Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks International Education Unit Law Medicine Music Online Products & Publishing Oxford Bibliographies Online Oxford Dictionaries Online Oxford English Dictionary Oxford Language Dictionaries Online Oxford Scholarship Online Reference Rights and Permissions Resources for Retailers & Wholesalers Resources for the Healthcare Industry Very Short Introductions World's Classics function fnc_onDomLoaded() { var query_context = getQueryContext(); PF_initOIUnderbar(query_context,":QS:default","","JRN"); PF_insertOIUnderbar(0); }; if (window.addEventListener) { window.addEventListener('load', fnc_onDomLoaded, false); } else if (window.attachEvent) { window.attachEvent('onload', fnc_onDomLoaded); } var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); try { var pageTracker = _gat._getTracker("UA-189672-16"); pageTracker._setDomainName(".oxfordjournals.org"); pageTracker._trackPageview(); } catch(err) {}

Journal

CarcinogenesisOxford University Press

Published: Aug 1, 1996

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