Arsenic compounds activate MAPK and inhibit Akt pathways to induce apoptosis in MA‐10 mouse Leydig tumor cells

Abstract Arsenic compounds have been applied treating acute promyelocytic 1eukemia and solid tumors with brief mechanism investigations. In fact, we have demonstrated that sodium arsenite plus dimethylarsenic acid could activate apoptosis in MA‐10 mouse Leydig tumor cells by inducing caspase pathway...

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Main Authors: Wei‐Sheng Juan, Yi‐Fen Mu, Chia‐Yih Wang, Edmund‐Cheung So, Yi‐Ping Lee, Sheng‐Che Lin, Bu‐Miin Huang
Format: Article
Language:English
Published: Wiley 2023-02-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.5068
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author Wei‐Sheng Juan
Yi‐Fen Mu
Chia‐Yih Wang
Edmund‐Cheung So
Yi‐Ping Lee
Sheng‐Che Lin
Bu‐Miin Huang
author_facet Wei‐Sheng Juan
Yi‐Fen Mu
Chia‐Yih Wang
Edmund‐Cheung So
Yi‐Ping Lee
Sheng‐Che Lin
Bu‐Miin Huang
author_sort Wei‐Sheng Juan
collection DOAJ
description Abstract Arsenic compounds have been applied treating acute promyelocytic 1eukemia and solid tumors with brief mechanism investigations. In fact, we have demonstrated that sodium arsenite plus dimethylarsenic acid could activate apoptosis in MA‐10 mouse Leydig tumor cells by inducing caspase pathways. However, detail underlying mechanisms how caspase cascade is regulated remains elusive. Therefore, the apoptotic mechanism of sodium arsenite plus dimethylarsenic acid were examined in MA‐10 cells in this study. Our results reveal that Fas/FasL protein expressions were stimulated by sodium arsenite plus dimethylarsenic acid in MA‐10 cells. In addition, reactive oxygen species (ROS) generation, cytochrome C release, Bid truncation, and Bax translocation were induced in MA‐10 cells by arsenic compounds. Moreover, activation of p38, JNK and ERK1/2, MAPK pathways was stimulated while Akt phosphorylated levels and Akt expression were decreased by sodium arsenite plus dimethylarsenic in MA‐10 cells. In conclusion, sodium arsenite and dimethylarsenic acid did activate MAPK pathway plus ROS generation, but suppress Akt pathway, to modulate caspase pathway and then induce MA‐10 cell apoptosis.
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spelling doaj-art-50bcb6f030d241d2855a66a19578d65d2025-08-20T01:53:22ZengWileyCancer Medicine2045-76342023-02-011233260327510.1002/cam4.5068Arsenic compounds activate MAPK and inhibit Akt pathways to induce apoptosis in MA‐10 mouse Leydig tumor cellsWei‐Sheng Juan0Yi‐Fen Mu1Chia‐Yih Wang2Edmund‐Cheung So3Yi‐Ping Lee4Sheng‐Che Lin5Bu‐Miin Huang6Department of Neurosurgery, An Nan Hospital China Medical University Tainan City TaiwanDepartment of Cell Biology and Anatomy, College of Medicine National Cheng Kung University Tainan TaiwanDepartment of Cell Biology and Anatomy, College of Medicine National Cheng Kung University Tainan TaiwanDepartment of Anesthesia & Medical Research, An Nan Hospital China Medical University Tainan City TaiwanDepartment of Cell Biology and Anatomy, College of Medicine National Cheng Kung University Tainan TaiwanDepartment of Plastic Surgical, An Nan Hospital China Medical University Tainan City TaiwanDepartment of Cell Biology and Anatomy, College of Medicine National Cheng Kung University Tainan TaiwanAbstract Arsenic compounds have been applied treating acute promyelocytic 1eukemia and solid tumors with brief mechanism investigations. In fact, we have demonstrated that sodium arsenite plus dimethylarsenic acid could activate apoptosis in MA‐10 mouse Leydig tumor cells by inducing caspase pathways. However, detail underlying mechanisms how caspase cascade is regulated remains elusive. Therefore, the apoptotic mechanism of sodium arsenite plus dimethylarsenic acid were examined in MA‐10 cells in this study. Our results reveal that Fas/FasL protein expressions were stimulated by sodium arsenite plus dimethylarsenic acid in MA‐10 cells. In addition, reactive oxygen species (ROS) generation, cytochrome C release, Bid truncation, and Bax translocation were induced in MA‐10 cells by arsenic compounds. Moreover, activation of p38, JNK and ERK1/2, MAPK pathways was stimulated while Akt phosphorylated levels and Akt expression were decreased by sodium arsenite plus dimethylarsenic in MA‐10 cells. In conclusion, sodium arsenite and dimethylarsenic acid did activate MAPK pathway plus ROS generation, but suppress Akt pathway, to modulate caspase pathway and then induce MA‐10 cell apoptosis.https://doi.org/10.1002/cam4.5068Aktdimethylarsenic acidLeydig tumor cellMAPKROSsodium arsenite
spellingShingle Wei‐Sheng Juan
Yi‐Fen Mu
Chia‐Yih Wang
Edmund‐Cheung So
Yi‐Ping Lee
Sheng‐Che Lin
Bu‐Miin Huang
Arsenic compounds activate MAPK and inhibit Akt pathways to induce apoptosis in MA‐10 mouse Leydig tumor cells
Cancer Medicine
Akt
dimethylarsenic acid
Leydig tumor cell
MAPK
ROS
sodium arsenite
title Arsenic compounds activate MAPK and inhibit Akt pathways to induce apoptosis in MA‐10 mouse Leydig tumor cells
title_full Arsenic compounds activate MAPK and inhibit Akt pathways to induce apoptosis in MA‐10 mouse Leydig tumor cells
title_fullStr Arsenic compounds activate MAPK and inhibit Akt pathways to induce apoptosis in MA‐10 mouse Leydig tumor cells
title_full_unstemmed Arsenic compounds activate MAPK and inhibit Akt pathways to induce apoptosis in MA‐10 mouse Leydig tumor cells
title_short Arsenic compounds activate MAPK and inhibit Akt pathways to induce apoptosis in MA‐10 mouse Leydig tumor cells
title_sort arsenic compounds activate mapk and inhibit akt pathways to induce apoptosis in ma 10 mouse leydig tumor cells
topic Akt
dimethylarsenic acid
Leydig tumor cell
MAPK
ROS
sodium arsenite
url https://doi.org/10.1002/cam4.5068
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AT chiayihwang arseniccompoundsactivatemapkandinhibitaktpathwaystoinduceapoptosisinma10mouseleydigtumorcells
AT edmundcheungso arseniccompoundsactivatemapkandinhibitaktpathwaystoinduceapoptosisinma10mouseleydigtumorcells
AT yipinglee arseniccompoundsactivatemapkandinhibitaktpathwaystoinduceapoptosisinma10mouseleydigtumorcells
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