Avarol Induces Apoptosis in Pancreatic Ductal Adenocarcinoma Cells by Activating PERK–eIF2α–CHOP Signaling
Avarol is a sesquiterpenoid hydroquinone with potent cytotoxicity. Although resolving endoplasmic reticulum (ER) stress is essential for intracellular homeostasis, erratic or excessive ER stress can lead to apoptosis. Here, we reported that avarol selectively induces cell death in pancreatic ductal...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-04-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/13/4/2376 |
| _version_ | 1798039288731926528 |
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| author | Takushi Namba Rika Kodama |
| author_facet | Takushi Namba Rika Kodama |
| author_sort | Takushi Namba |
| collection | DOAJ |
| description | Avarol is a sesquiterpenoid hydroquinone with potent cytotoxicity. Although resolving endoplasmic reticulum (ER) stress is essential for intracellular homeostasis, erratic or excessive ER stress can lead to apoptosis. Here, we reported that avarol selectively induces cell death in pancreatic ductal adenocarcinomas (PDAC), which are difficult to treat owing to the availability of few chemotherapeutic agents. Analyses of the molecular mechanisms of avarol-induced apoptosis indicated upregulation of ER stress marker BiP and ER stress-dependent apoptosis inducer CHOP in PDAC cells but not in normal cells, suggesting that avarol selectively induces ER stress responses. We also showed that avarol activated the PERK–eIF2α pathway but did not affect the IRE1 and ATF6 pathways. Moreover, CHOP downregulation was significantly suppressed by avarol-induced apoptosis. Thus, the PERK–eIF2α–CHOP signaling pathway may be a novel molecular mechanism of avarol-induced apoptosis. The present data indicate that avarol has potential as a chemotherapeutic agent for PDAC and induces apoptosis by activating the PERK–eIF2α pathway. |
| first_indexed | 2024-04-11T21:51:49Z |
| format | Article |
| id | doaj.art-fbe4da1f6afa4546ac646a82bec6a36c |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-04-11T21:51:49Z |
| publishDate | 2015-04-01 |
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| series | Marine Drugs |
| spelling | doaj.art-fbe4da1f6afa4546ac646a82bec6a36c2022-12-22T04:01:13ZengMDPI AGMarine Drugs1660-33972015-04-011342376238910.3390/md13042376md13042376Avarol Induces Apoptosis in Pancreatic Ductal Adenocarcinoma Cells by Activating PERK–eIF2α–CHOP SignalingTakushi Namba0Rika Kodama1Science Research Center, Kochi University, Kohasu, Oko-cho, Nankoku-shi, Kochi 783-8505, JapanScience Research Center, Kochi University, Kohasu, Oko-cho, Nankoku-shi, Kochi 783-8505, JapanAvarol is a sesquiterpenoid hydroquinone with potent cytotoxicity. Although resolving endoplasmic reticulum (ER) stress is essential for intracellular homeostasis, erratic or excessive ER stress can lead to apoptosis. Here, we reported that avarol selectively induces cell death in pancreatic ductal adenocarcinomas (PDAC), which are difficult to treat owing to the availability of few chemotherapeutic agents. Analyses of the molecular mechanisms of avarol-induced apoptosis indicated upregulation of ER stress marker BiP and ER stress-dependent apoptosis inducer CHOP in PDAC cells but not in normal cells, suggesting that avarol selectively induces ER stress responses. We also showed that avarol activated the PERK–eIF2α pathway but did not affect the IRE1 and ATF6 pathways. Moreover, CHOP downregulation was significantly suppressed by avarol-induced apoptosis. Thus, the PERK–eIF2α–CHOP signaling pathway may be a novel molecular mechanism of avarol-induced apoptosis. The present data indicate that avarol has potential as a chemotherapeutic agent for PDAC and induces apoptosis by activating the PERK–eIF2α pathway.http://www.mdpi.com/1660-3397/13/4/2376avarolER stresspancreatic ductal adenocarcinomasCHOP |
| spellingShingle | Takushi Namba Rika Kodama Avarol Induces Apoptosis in Pancreatic Ductal Adenocarcinoma Cells by Activating PERK–eIF2α–CHOP Signaling Marine Drugs avarol ER stress pancreatic ductal adenocarcinomas CHOP |
| title | Avarol Induces Apoptosis in Pancreatic Ductal Adenocarcinoma Cells by Activating PERK–eIF2α–CHOP Signaling |
| title_full | Avarol Induces Apoptosis in Pancreatic Ductal Adenocarcinoma Cells by Activating PERK–eIF2α–CHOP Signaling |
| title_fullStr | Avarol Induces Apoptosis in Pancreatic Ductal Adenocarcinoma Cells by Activating PERK–eIF2α–CHOP Signaling |
| title_full_unstemmed | Avarol Induces Apoptosis in Pancreatic Ductal Adenocarcinoma Cells by Activating PERK–eIF2α–CHOP Signaling |
| title_short | Avarol Induces Apoptosis in Pancreatic Ductal Adenocarcinoma Cells by Activating PERK–eIF2α–CHOP Signaling |
| title_sort | avarol induces apoptosis in pancreatic ductal adenocarcinoma cells by activating perk eif2α chop signaling |
| topic | avarol ER stress pancreatic ductal adenocarcinomas CHOP |
| url | http://www.mdpi.com/1660-3397/13/4/2376 |
| work_keys_str_mv | AT takushinamba avarolinducesapoptosisinpancreaticductaladenocarcinomacellsbyactivatingperkeif2achopsignaling AT rikakodama avarolinducesapoptosisinpancreaticductaladenocarcinomacellsbyactivatingperkeif2achopsignaling |