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Corynoxine and corynoxine B enhance the antitumor activity of gemcitabine in Panc-1 cells via ROS-p38 signaling pathway

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Title Corynoxine and corynoxine B enhance the antitumor activity of gemcitabine in Panc-1 cells via ROS-p38 signaling pathway
 
Creator Yin, Limin
Shi, Chaohong
Zhang, Zhongchen
Wang, Wensheng
Li, Ming
 
Subject p38
Pancreatic ductal adenocarcinoma
Reactvie oxygen species (ROS)
 
Description 614-621
Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors, and effective therapeutic interventions for PDAC are limited. While Corynoxine (Cory) and its isomer Cory B have been identified as autophagy inducers in neuronal cells, it remains unclear whether they exert a therapeutic effect on PDAC. Here, we performed cell counting kit-8 (CCK8), colony formation, 5-Ethynyl-2′-deoxyuridine (EDU) staining, TUNEL, and flow cytometry assays to evaluate the effects of Cory on PDAC. Western blotting was conducted to analyze the protein expression levels. We showed that Cory and Cory B enhanced cell growth arrest and pro-apoptotic effects of gemcitabine (Gem) on Gem-resistant Panc-1 cells. Mechanistic studies revealed that increased production of reactive oxygen species (ROS) and p38 activation were closely associated with Cory and Cory B-induced cell death. Pretreatment with ROS scavenger N-acetylcysteine blocked Cory and Cory B-induced cell death. Moreover, p38 inhibitor SB203580 prevented cell death induced by Cory and Cory B. Overall, Cory and Cory B increase the sensitivity of Gem-resistant Panc-1 cells to Gem through the activation of ROS-dependent p38 signaling pathway. Our results indicate that Cory and Cory B might be potential approaches for PDAC therapy.
 
Date 2023-07-31T10:04:41Z
2023-07-31T10:04:41Z
2023-07
 
Type Article
 
Identifier 0975-1009 (Online); 0019-5189 (Print)
http://nopr.niscpr.res.in/handle/123456789/62384
https://doi.org/10.56042/ijeb.v61i08.3878
 
Language en
 
Publisher NIScPR-CSIR,India
 
Source IJEB Vol.61(08) [August 2023]