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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doaj-81f77f549a834a34b8542d80d7ba3f6a2020-11-25T00:47:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9262710.1371/journal.pone.0092627Melatonin combined with endoplasmic reticulum stress induces cell death via the PI3K/Akt/mTOR pathway in B16F10 melanoma cells.Han Sung KimTack-Joong KimYeong-Min YooThis 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.http://europepmc.org/articles/PMC3960269?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Han Sung Kim Tack-Joong Kim Yeong-Min Yoo |
spellingShingle |
Han Sung Kim Tack-Joong Kim Yeong-Min Yoo Melatonin combined with endoplasmic reticulum stress induces cell death via the PI3K/Akt/mTOR pathway in B16F10 melanoma cells. PLoS ONE |
author_facet |
Han Sung Kim Tack-Joong Kim Yeong-Min Yoo |
author_sort |
Han Sung Kim |
title |
Melatonin combined with endoplasmic reticulum stress induces cell death via the PI3K/Akt/mTOR pathway in B16F10 melanoma cells. |
title_short |
Melatonin combined with endoplasmic reticulum stress induces cell death via the PI3K/Akt/mTOR pathway in B16F10 melanoma cells. |
title_full |
Melatonin combined with endoplasmic reticulum stress induces cell death via the PI3K/Akt/mTOR pathway in B16F10 melanoma cells. |
title_fullStr |
Melatonin combined with endoplasmic reticulum stress induces cell death via the PI3K/Akt/mTOR pathway in B16F10 melanoma cells. |
title_full_unstemmed |
Melatonin combined with endoplasmic reticulum stress induces cell death via the PI3K/Akt/mTOR pathway in B16F10 melanoma cells. |
title_sort |
melatonin combined with endoplasmic reticulum stress induces cell death via the pi3k/akt/mtor pathway in b16f10 melanoma cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
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. |
url |
http://europepmc.org/articles/PMC3960269?pdf=render |
work_keys_str_mv |
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