Melatonin combined with endoplasmic reticulum stress induces cell death via the PI3K/Akt/mTOR pathway in B16F10 melanoma cells

This study investigated B16F10 melanoma cell death induced by melatonin combined with endoplasmic reticulum (ER) stress through the PI3K/Akt/mTOR pathway. Cell viability was significantly decreased after treatment with melatonin combined with ER stress from thapsigargin or tunicamycin compared to no...

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Published in:PloS one 2014-03, Vol.9 (3), p.e92627-e92627
Main Authors: Kim, Han Sung, Kim, Tack-Joong, Yoo, Yeong-Min
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
AKT protein
Animals
Apoptosis
BAX protein
Bcl-2 protein
Biochemistry
Biology and life sciences
Biomedical engineering
Biotechnology
Cancer therapies
Catalase
Cell death
Cell Death - physiology
Cell Line, Tumor
Cell survival
Cell Survival - drug effects
Combined treatment
Comparative analysis
Copper
Endoplasmic reticulum
Endoplasmic Reticulum Stress - drug effects
Endoplasmic Reticulum Stress - genetics
Endoplasmic Reticulum Stress - physiology
Inhibitors
Investigations
Kinases
Lymphoma
Manganese
Medicine and Health Sciences
Melanoma
Melatonin
Melatonin - pharmacology
Phosphatidylinositol 3-Kinases - genetics
Phosphatidylinositol 3-Kinases - metabolism
Proteins
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - metabolism
Rodents
Science
Skin cancer
Stress
Stresses
Superoxides
Thapsigargin
TOR protein
TOR Serine-Threonine Kinases - genetics
TOR Serine-Threonine Kinases - metabolism
Tumors
Tunicamycin
Wortmannin
Zinc
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Kim, Tack-Joong
Yoo, Yeong-Min
description This study investigated B16F10 melanoma cell death induced by melatonin combined with endoplasmic reticulum (ER) stress through the PI3K/Akt/mTOR pathway. Cell viability was significantly decreased after treatment with melatonin combined with ER stress from thapsigargin or tunicamycin compared to no treatment or treatment with melatonin only. Combined melatonin and ER stress also significantly reduced expression of p85β, p-Akt (Ser473, Thr308), and p-mTOR (Ser2448, Ser2481) compared to treatment with melatonin only. The ER stress protein p-PERK and p-eIF2α were significantly increased under combined melatonin and ER stress treatment compared to no treatment or treatment with melatonin only. Combined melatonin and ER stress significantly reduced Bcl-2 protein and augmented Bax protein compared to melatonin-only treatment. Also, the combined treatment significantly lowered expression of catalase, Cu/Zn-SOD, and Mn-SOD proteins compared to melatonin only. Expression of p85β was significantly more decreased under treatment with melatonin and thapsigargin or tunicamycin plus the PI3K inhibitors LY294002 or wortmannin than under treatment with only melatonin or a PI3K inhibitor. The PI3K downstream target p-Akt (Ser473, Thr308) showed significantly decreased expression under treatment with melatonin and thapsigargin or tunicamycin plus PI3K inhibitors than under treatment with melatonin or PI3K inhibitors only. These results indicate that survival of B16F10 melanoma cells after combined treatment with melatonin and ER stress inducers is suppressed through regulation of the PI3K/Akt/mTOR pathway. Melatonin combined with thapsigargin or tunicamycin appears to be a promising strategy for effective melanoma treatment.
doi_str_mv 10.1371/journal.pone.0092627
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Cell viability was significantly decreased after treatment with melatonin combined with ER stress from thapsigargin or tunicamycin compared to no treatment or treatment with melatonin only. Combined melatonin and ER stress also significantly reduced expression of p85β, p-Akt (Ser473, Thr308), and p-mTOR (Ser2448, Ser2481) compared to treatment with melatonin only. The ER stress protein p-PERK and p-eIF2α were significantly increased under combined melatonin and ER stress treatment compared to no treatment or treatment with melatonin only. Combined melatonin and ER stress significantly reduced Bcl-2 protein and augmented Bax protein compared to melatonin-only treatment. Also, the combined treatment significantly lowered expression of catalase, Cu/Zn-SOD, and Mn-SOD proteins compared to melatonin only. 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physiology</topic><topic>Cell Line, Tumor</topic><topic>Cell survival</topic><topic>Cell Survival - drug effects</topic><topic>Combined treatment</topic><topic>Comparative analysis</topic><topic>Copper</topic><topic>Endoplasmic reticulum</topic><topic>Endoplasmic Reticulum Stress - drug effects</topic><topic>Endoplasmic Reticulum Stress - genetics</topic><topic>Endoplasmic Reticulum Stress - physiology</topic><topic>Inhibitors</topic><topic>Investigations</topic><topic>Kinases</topic><topic>Lymphoma</topic><topic>Manganese</topic><topic>Medicine and Health Sciences</topic><topic>Melanoma</topic><topic>Melatonin</topic><topic>Melatonin - pharmacology</topic><topic>Phosphatidylinositol 3-Kinases - genetics</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - genetics</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Rodents</topic><topic>Science</topic><topic>Skin cancer</topic><topic>Stress</topic><topic>Stresses</topic><topic>Superoxides</topic><topic>Thapsigargin</topic><topic>TOR protein</topic><topic>TOR Serine-Threonine Kinases - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Han Sung</au><au>Kim, Tack-Joong</au><au>Yoo, Yeong-Min</au><au>Mohanraj, Rajesh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Melatonin combined with endoplasmic reticulum stress induces cell death via the PI3K/Akt/mTOR pathway in B16F10 melanoma cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-03-19</date><risdate>2014</risdate><volume>9</volume><issue>3</issue><spage>e92627</spage><epage>e92627</epage><pages>e92627-e92627</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>This study investigated B16F10 melanoma cell death induced by melatonin combined with endoplasmic reticulum (ER) stress through the PI3K/Akt/mTOR pathway. Cell viability was significantly decreased after treatment with melatonin combined with ER stress from thapsigargin or tunicamycin compared to no treatment or treatment with melatonin only. Combined melatonin and ER stress also significantly reduced expression of p85β, p-Akt (Ser473, Thr308), and p-mTOR (Ser2448, Ser2481) compared to treatment with melatonin only. The ER stress protein p-PERK and p-eIF2α were significantly increased under combined melatonin and ER stress treatment compared to no treatment or treatment with melatonin only. Combined melatonin and ER stress significantly reduced Bcl-2 protein and augmented Bax protein compared to melatonin-only treatment. Also, the combined treatment significantly lowered expression of catalase, Cu/Zn-SOD, and Mn-SOD proteins compared to melatonin only. Expression of p85β was significantly more decreased under treatment with melatonin and thapsigargin or tunicamycin plus the PI3K inhibitors LY294002 or wortmannin than under treatment with only melatonin or a PI3K inhibitor. The PI3K downstream target p-Akt (Ser473, Thr308) showed significantly decreased expression under treatment with melatonin and thapsigargin or tunicamycin plus PI3K inhibitors than under treatment with melatonin or PI3K inhibitors only. These results indicate that survival of B16F10 melanoma cells after combined treatment with melatonin and ER stress inducers is suppressed through regulation of the PI3K/Akt/mTOR pathway. Melatonin combined with thapsigargin or tunicamycin appears to be a promising strategy for effective melanoma treatment.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24647338</pmid><doi>10.1371/journal.pone.0092627</doi><tpages>e92627</tpages><oa>free_for_read</oa></addata></record>
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1932-6203
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subjects 1-Phosphatidylinositol 3-kinase
AKT protein
Animals
Apoptosis
BAX protein
Bcl-2 protein
Biochemistry
Biology and life sciences
Biomedical engineering
Biotechnology
Cancer therapies
Catalase
Cell death
Cell Death - physiology
Cell Line, Tumor
Cell survival
Cell Survival - drug effects
Combined treatment
Comparative analysis
Copper
Endoplasmic reticulum
Endoplasmic Reticulum Stress - drug effects
Endoplasmic Reticulum Stress - genetics
Endoplasmic Reticulum Stress - physiology
Inhibitors
Investigations
Kinases
Lymphoma
Manganese
Medicine and Health Sciences
Melanoma
Melatonin
Melatonin - pharmacology
Phosphatidylinositol 3-Kinases - genetics
Phosphatidylinositol 3-Kinases - metabolism
Proteins
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - metabolism
Rodents
Science
Skin cancer
Stress
Stresses
Superoxides
Thapsigargin
TOR protein
TOR Serine-Threonine Kinases - genetics
TOR Serine-Threonine Kinases - metabolism
Tumors
Tunicamycin
Wortmannin
Zinc
title Melatonin combined with endoplasmic reticulum stress induces cell death via the PI3K/Akt/mTOR pathway in B16F10 melanoma cells
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T18%3A25%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Melatonin%20combined%20with%20endoplasmic%20reticulum%20stress%20induces%20cell%20death%20via%20the%20PI3K/Akt/mTOR%20pathway%20in%20B16F10%20melanoma%20cells&rft.jtitle=PloS%20one&rft.au=Kim,%20Han%20Sung&rft.date=2014-03-19&rft.volume=9&rft.issue=3&rft.spage=e92627&rft.epage=e92627&rft.pages=e92627-e92627&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0092627&rft_dat=%3Cgale_plos_%3EA478758809%3C/gale_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c692t-2124481f90b009ba8a642273ee1496b8008b17ac1a9005f59574c64aa7e3504c3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1508765755&rft_id=info:pmid/24647338&rft_galeid=A478758809&rfr_iscdi=true