scholarly journals Chemopreventive Effects of Dietary Isothiocyanates in Animal Models of Gastric Cancer and Synergistic Anticancer Effects With Cisplatin in Human Gastric Cancer Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Hanne-Line Rabben ◽  
Yosuke Kodama ◽  
Masahiko Nakamura ◽  
Atle Magnar Bones ◽  
Timothy Cragin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mouse Model ◽  
Cancer Cells ◽  
Genetically Engineered ◽  
Human Gastric Cancer ◽  
M Cell ◽  
Gastric Cancer Cells ◽  
Combination Strategy ◽  
Genetically Engineered Mouse Model ◽  
Anti Cancer

Naturally occurring isothiocyanates (ITCs) from edible vegetables have shown potential as chemopreventive agents against several types of cancer. The aims of the present study were to study the potential of ITCs in chemoprevention and in potentiating the efficacy of cytotoxic drugs in gastric cancer treatment. The chemoprevention was studied in chemically induced mouse model of gastric cancer, namely N-methyl-N-nitrosourea (MNU) in drinking water, and in a genetically engineered mouse model of gastric cancer (the so-called INS-GAS mice). The pharmacological effects of ITCs with or without cisplatin were studied in human gastric cell lines MKN45, AGS, MKN74 and KATO-III, which were derived from either intestinal or diffused types of gastric carcinoma. The results showed that dietary phenethyl isothiocyanate (PEITC) reduced the tumor size when PEITC was given simultaneously with MNU, but neither when administrated after MNU nor in INS-GAS mice. Treatments of gastric cancer cells with ITCs resulted in a time- and concentration-dependent inhibition on cell proliferation. Pretreatment of gastric cancer cells with ITCs enhanced the inhibitory effects of cisplatin (but not 5-fluorouracil) in time- and concentration-dependent manners. Treatments of gastric cancer cells with PEITC plus cisplatin simultaneously at different concentrations of either PEITC or cisplatin exhibited neither additive nor synergetic inhibitory effect. Furthermore, PEITC depleted glutathione and induced G2/M cell cycle arrest in gastric cancer cells. In conclusion, the results of the present study showed that PEITC displayed anti-cancer effects, particularly when given before the tumor initiation, suggesting a chemopreventive effect in gastric cancer, and that pretreatment of PEITC potentiated the anti-cancer effects of cisplatin, possibly by reducing the intracellular pool of glutathione, suggesting a possible combination strategy of chemotherapy with pretreatment with PEITC.

scholarly journals Ailanthone induces G2/M cell cycle arrest and apoptosis of SGC-7901 human gastric cancer cells

2017 ◽  
Vol 16 (5) ◽  
pp. 6821-6827 ◽  
Author(s):  
Yuxin Chen ◽  
Ling Zhu ◽  
Xi Yang ◽  
Cheng Wei ◽  
Chuanrong Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Human Gastric Cancer ◽  
M Cell ◽  
Gastric Cancer Cells ◽  
Cycle Arrest

scholarly journals Gramicidin inhibits human gastric cancer cell proliferation, cell cycle and induced apoptosis

2019 ◽  
Vol 52 (1) ◽  
Author(s):  
Tingting Chen ◽  
Yong Wang ◽  
Yang Yang ◽  
Kaikai Yu ◽  
Xiangliao Cao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
High Morbidity ◽  
Peptide Antibiotic ◽  
Human Gastric Cancer ◽  
M Cell ◽  
Gastric Cancer Cells ◽  
Gastric Mucosal Cells ◽  
Mucosal Cells

Abstract Background Gastric cancer is a common malignant tumor with high morbidity and mortality worldwide, which seriously affects human health. Gramicidin is a short peptide antibiotic which could be used for treating infection induced by bacteria or fungi. However, the anti-cancer effect of gramicidin on gastric cancer cells and its underlying mechanism remains largely unknown. Results Gastric cancer cells SGC-7901, BGC-823 and normal gastric mucosal cells GES-1 were treated with different concentrations of gramicidin respectively. The results of CCK-8 experiment revealed cellular toxicity of gramicidin to cancer cells while cell colony formation assay showed that gramicidin significantly inhibited the proliferation of gastric cancer cells, but had little effect on normal gastric mucosal cells. In addition, the wound healing assay showed that gramicidin inhibited the migration of SGC-7901 cell. Meanwhile, apoptosis and cell cycle analysis revealed that gramicidin induced cell apoptosis with G2/M cell cycle inhibition. Furthermore, western blot analysis demonstrated that gramicidin down-regulated the expression of cyclinD1 and Bcl-2 as well as the FoxO1 phosphorylation. Conclusions The current study illustrated the anti-tumor activity of gramicidin on gastric cancer cells, providing a possibility for gramicidin to be applied in clinical practice for the treatment of gastric cancer.

scholarly journals Bufalin inhibits the growth and epithelial to mesenchymal transition of human gastric cancer cells via modulation of MEK/ERK pathway

2021 ◽  
Vol 16 (1) ◽  
pp. 27-33
Author(s):  
Yi Zhou ◽  
Liguo Wang ◽  
Hui Lin ◽  
Yunxia Wang ◽  
Kezhu Hou
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Human Gastric Cancer ◽  
M Cell ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Cycle Arrest

This study was designed to evaluate the anti-cancer effects of bufalin against the human gastric cancer cells and unveil the underlying mechanism. The results showed that bufalin inhibited the proliferation and colony formation of the MGC-803 gastric cancer cells and exhibited an IC50 of 10 μM. These antiproliferative effects were found to be due to the induction of G2/M cell cycle arrest. The G2/M cell cycle arrest was also concomitant with inhibition of cdc2, cdc25 and cyclin B1. Furthermore, bufalin suppressed the epithelial-to-mesenchymal transition, migration, and invasion of the MGC-803 gastric cancer cells. The Western blot analysis revealed that bufalin exerted its effects via deactivation of EK/ERK signaling pathway. Taken together, these results suggest the potential of bufalin as the lead molecule for the development of chemotherapy for gastric cancer.  

scholarly journals The p62/Keap1/Nrf2 axis in the control of C-2 induced human gastric cancer cell death switching between autophagy and apoptosis

2021 ◽  
Author(s):  
ZhenYa Wang ◽  
Yong Guo ◽  
En Zhang ◽  
QianHong Ban ◽  
MengLin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Target Genes ◽  
Beclin 1 ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Compound C ◽  
Anti Cancer ◽  
Cancer Activity

Abstract Background Compound C-2 is a derivative of natural product Jaspine B and possesses anti-cancer activity against bladder cancer cells. However, little is known about its anti-cancer activity against gastric cancer. In this research, mechanism underlying anti-cancer effect of C-2 in gastric cancer cells was well investigated. Methods Anti-cancer activities of C-2 were determined by MTT, western blotting and flow cytometry. A serial of specific inhibitors, immunoprecipitation, siRNA and immunofluorescence were utilized to explore signaling pathways affected by C-2. Results C-2 induces apoptosis in gastric cancer cells through the internal mitochondrial pathway, and triggers autophagy in gastric cancer cells through JNK/ERK pathway. Phosphorylated JNK/ERK further activates Beclin1 via disturbing Beclin-1/Bcl-xL or Beclin-1/Bcl-2 complexes, leading to autophagy and up-regulated p62. Next, p62 competitively binds keap1 to release Nrf2, thus promoting translocation of Nrf2 from cytoplasm to nucleus and triggering expression of Nrf2 target genes. Pharmacological inhibition or knockdown of key proteins in autophagy attenuates C-2 induced cell apoptosis, indicating that autophagy antagonizes cell apoptosis induced by C-2. Conclusion C-2 possesses anti-tumor activity against gastric cancer cells, while C-2 triggered-autophagy antagonizes cell arrest and apoptosis induced by C-2 by upregulating Nrf2 in nucleus.

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