Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Autophagy Induction by Capsaicin in Malignant Human Breast Cells Is Modulated by p38 and Extracellular Signal-Regulated Mitogen-Activated Protein Kinases and Retards Cell Death by Suppressing Endoplasmic Reticulum Stress-Mediated Apoptosis

Cheol-Hee Choi, Yong-Keun Jung and Seon-Hee Oh
Molecular Pharmacology July 2010, 78 (1) 114-125; DOI: https://doi.org/10.1124/mol.110.063495
Cheol-Hee Choi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yong-Keun Jung
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Seon-Hee Oh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

In our previous study, we showed that capsaicin induces autophagy in several cell lines. Here, we investigated the molecular mechanisms of capsaicin-induced autophagy in malignant (MCF-7 and MDA-MB-231) and normal (MCF10A) human breast cells. Capsaicin caused nonapoptotic cell cycle arrest of MCF-7 and MDA-MB-231 cells but induced apoptosis in MCF10A cells. In MCF-7 and MDA-MB-231 cells, capsaicin induced endoplasmic reticulum (ER) stress via inositol-requiring 1 and Chop and induced autophagy, as demonstrated by microtubule-associated protein 1 light chain-3 (LC3) conversion. Autophagy blocking by 3-methyladenine (3MA) or bafilomycin A1 (BaF1) activated caspase-4 and -7 and enhanced cell death. In MCF-7 and MDA-MB-231 cells, p38 was activated for more than 48 h by capsaicin treatment, but extracellular signal-regulated kinase (ERK) activation decreased after 12 h, and LC3II levels continuously increased. Furthermore, treatment with 3MA markedly down-regulated capsaicin-induced p38 activation and LC3 conversion, and BaF1 completely down-regulated ERK activation and led to LC3II accumulation. In addition, pharmacological blockade or knockdown of the p38 gene down-regulated Akt activation and LC3II levels but did not affect ERK, and pharmacological blockade or knockdown of the ERK gene up-regulated LC3II induction by capsaicin. Knockdown of inositol-requiring 1 down-regulated p38-Akt signaling. In MCF10A cells, capsaicin did not elicit p38 activation and LC3 conversion and caused the sustained activation of caspase-4. Collectively, capsaicin-induced autophagy is regulated by p38 and ERK; p38 controls autophagy at the sequestration step, whereas ERK controls autophagy at the maturation step, and that autophagy is involved in the retardation of cell death by blocking capsaicin-induced ER stress-mediated apoptosis in MCF-7 and MDA-MB-321 cells.

Footnotes

  • ↵Embedded Image The online version of this article (available at http://molpharm.aspetjournals.org) contains supplemental material.

  • This work was supported by the National Research Foundation of Korea, funded by the Ministry of Education, Science, and Technology through the Research Center for Resistant Cells [Grant R13-2003-009].

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.110.063495.

  • ABBREVIATIONS:

    UPR
    unfolded protein response
    ER
    endoplasmic reticulum
    IRE1
    inositol-requiring enzyme 1
    LC3
    microtubule-associated protein 1 light chain-3
    MAPK
    mitogen-activated protein kinase
    3MA
    3-methyladenine
    BaF1
    bafilomycin A1
    ERK
    extracellular-regulated kinase
    MTT
    3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
    DMSO
    dimethyl sulfoxide
    PBS
    phosphate-buffered saline
    JNK
    c-Jun N-terminal kinase
    siRNA
    short interfering RNA
    LY294002
    2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride
    PD98059
    2′-amino-3′-methoxyflavone
    SB203580
    4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole
    EB1089
    seocalcitol.

  • Received January 7, 2010.
  • Accepted April 6, 2010.
  • Copyright © 2010 The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 78 (1)
Molecular Pharmacology
Vol. 78, Issue 1
1 Jul 2010
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Autophagy Induction by Capsaicin in Malignant Human Breast Cells Is Modulated by p38 and Extracellular Signal-Regulated Mitogen-Activated Protein Kinases and Retards Cell Death by Suppressing Endoplasmic Reticulum Stress-Mediated Apoptosis
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Autophagy Induction by Capsaicin in Malignant Human Breast Cells Is Modulated by p38 and Extracellular Signal-Regulated Mitogen-Activated Protein Kinases and Retards Cell Death by Suppressing Endoplasmic Reticulum Stress-Mediated Apoptosis

Cheol-Hee Choi, Yong-Keun Jung and Seon-Hee Oh
Molecular Pharmacology July 1, 2010, 78 (1) 114-125; DOI: https://doi.org/10.1124/mol.110.063495

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Autophagy Induction by Capsaicin in Malignant Human Breast Cells Is Modulated by p38 and Extracellular Signal-Regulated Mitogen-Activated Protein Kinases and Retards Cell Death by Suppressing Endoplasmic Reticulum Stress-Mediated Apoptosis

Cheol-Hee Choi, Yong-Keun Jung and Seon-Hee Oh
Molecular Pharmacology July 1, 2010, 78 (1) 114-125; DOI: https://doi.org/10.1124/mol.110.063495
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Therapeutic Effects of FGF23 Antagonists in Hyp Mice
  • Secretin Amino-Terminal Structure-Activity Relationships and Complementary Mutagenesis at the Site of Docking to the Secretin Receptor
  • LYN Kinase and Tyrosine Kinase Inhibitors Regulate OATP1B3
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics