scholarly journals Dehydroabietic Acid Derivative QC4 Induces Gastric Cancer Cell Death via Oncosis and Apoptosis

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Dongjun Luo ◽  
Qing Ni ◽  
Anlai Ji ◽  
Wen Gu ◽  
Junhua Wu ◽  
...  

Aim. QC4 is the derivative of rosin’s main components dehydroabietic acid (DHA). We investigated the cytotoxic effect of QC4 on gastric cancer cells and revealed the mechanisms beneath the induction of cell death.Methods. The cytotoxic effect of QC4 on gastric cancer cells was evaluated by CCK-8 assay and flow cytometry. The underlying mechanisms were tested by administration of cell death related inhibitors and detection of apoptotic and oncosis related proteins. Cytomembrane integrity and organelles damage were confirmed by lactate dehydrogenase (LDH) leakage assay, mitochondrial function test, and cytosolic free Ca2+concentration detection.Results. QC4 inhibited cell proliferation dose- and time-dependently and destroyed cell membrane integrity, activated calpain-1 autolysis, and induced apoptotic protein cleavage in gastric cancer cells. The detection of decreased ATP and mitochondrial membrane potential, ROS accumulation, and cytosolic free Ca2+elevation confirmed organelles damage in QC4-treated gastric cancer cells.Conclusions. DHA derivative QC4 induced the damage of cytomembrane and organelles which finally lead to oncosis and apoptosis in gastric cancer cells. Therefore, as a derivative of plant derived small molecule DHA, QC4 might become a promising agent in gastric cancer therapy.

2013 ◽  
Vol 329 (2) ◽  
pp. 189-196 ◽  
Author(s):  
Minghui Chen ◽  
Le Yu ◽  
Chunping Gu ◽  
Desheng Zhong ◽  
Shuguang Wu ◽  
...  

Author(s):  
Silvia Yumnam ◽  
Suchismita Raha ◽  
Seong Kim ◽  
Venu Venkatarame Gowda Saralamma ◽  
Ho Lee ◽  
...  

2012 ◽  
Vol 90 (2) ◽  
pp. 175-186 ◽  
Author(s):  
Byung Joo Kim ◽  
Sung-Young Kim ◽  
Sanghoon Lee ◽  
Ju-Hong Jeon ◽  
Hirofumi Matsui ◽  
...  

Transient receptor potential cation channel, subfamily M, receptor 7 (TRPM7) is a ubiquitous divalent-selective ion channel with its own kinase domain. Human gastric cancer cells express the TRPM7 channel, and the presence of this channel is essential for cell survival. Recent studies have suggested that 5-lipoxygenase (5-LOX) inhibitors are potent blockers of the TRPM7 channels. The aim of this study was to show the effects of 5-LOX inhibitors on the growth and survival of gastric cancer cells. Among 5-LOX inhibitors, nordihydroguaiaretic acid (NDGA), 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861), and 3-[1-(p-chlorobenzyl)-5-(isopropyl)-3-tert-butylthioindol-2-yl]-2,2-dimethylpropanoic acid (MK886) were potent blockers of TRPM7-like currents in gastric cancer cells and also induced cell death. However, zileuton was ineffective in suppressing TRPM7-like current activity and inducing cell death. Moreover, a specific transient receptor potential cation channel, subfamily C, member 3 (TRPC3) inhibitor, a pyrazole compound (Pyr3), and a specific melastatin TRP (TRPM4) inhibitor, 9-phenanthrol, did not affect TRPM7-like currents or induce cell death. We conclude that TRPM7 has an important role in the growth and survival of gastric cancer cells and a likely potential target for the pharmacological treatment of gastric cancer.


Oncogene ◽  
1999 ◽  
Vol 18 (40) ◽  
pp. 5604-5609 ◽  
Author(s):  
Hiroyuki Okuda ◽  
Masaaki Adachi ◽  
Masaaki Miyazawa ◽  
Yuji Hinoda ◽  
Kohzoh Imai

2017 ◽  
Vol 9 ◽  
pp. 294-311 ◽  
Author(s):  
Bowen Li ◽  
Lu Wang ◽  
Zheng Li ◽  
Weizhi Wang ◽  
Xiaofei Zhi ◽  
...  

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