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.

scholarly journals Anti-HER2 monoclonal antibodies intensify the susceptibility of human gastric cancer cells to etoposide by promoting apoptosis, but not autophagy

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255585
Author(s):  
Agnieszka Gornowicz ◽  
Wojciech Szymanowski ◽  
Robert Czarnomysy ◽  
Krzysztof Bielawski ◽  
Anna Bielawska
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Flow Cytometry ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Beclin 1 ◽  
Proliferative Potential ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Promising Strategy

Background Gastric cancer (GC) is a multifactorial disease with high mortality. Anti-HER2 therapy is a promising strategy in GC treatment and trastuzumab was approved by FDA (Food and Drug Administration) as the first and the second line of treatment of the disease. Purpose The aim of the study was to examine the effectiveness of a combination of etoposide with trastuzumab or pertuzumab in AGS gastric cancer cells and breast cancer cells such as MCF-7, MDA-MB-231 and HCC1954. Methods and findings The cytotoxic effects of the tested compounds against gastric and breast cancer cells were checked by MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) assay. The anti-proliferative potential was analyzed by the incorporation of [3H]-thymidine into DNA. Fluorescent microscopy and flow cytometry was used to demonstrate the effect of the compounds on apoptosis. The mitochondrial membrane potential, and the activity of caspase-8 and caspase-9 were assessed. Autophagosomes and autolysosomes formation was checked by flow cytometry. The concentrations of Beclin-1, LC3A and LC3B were performed using ELISA. The expression of LC3A/B was also determined. The results from our study proved that the combination of etoposide with anti-HER2 antibodies was not cytotoxic against breast cancer cells, whereas the combination of etoposide with anti-HER2 antibodies decreased viability and DNA biosynthesis in gastric cancer cells. The interaction of etoposide with pertuzumab or trastuzumab induced programmed cell death via extrinsic and intrinsic apoptotic pathways in AGS gastric cancer cells, but did not affect autophagy, where a decrease of Beclin-1, LC3A and LC3B was observed in comparison with the untreated control. Conclusions The study demonstrated that etoposide (12.5 μM) with pertuzumab represent a promising strategy in gastric cancer treatment, but further in vivo examinations are also required.

scholarly journals AnnexinA5 Might Suppress the Phenotype of Human Gastric Cancer Cells via ERK Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaojie Wang ◽  
Yarui Dai ◽  
Yina Zhao ◽  
Meichuan Li ◽  
Jialu Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Signal Pathway ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Proliferation And Metastasis ◽  
Erk Signal Pathway ◽  
Apoptosis And Necrosis ◽  
Cell Proliferation And Metastasis

Gastric cancer is one of the most fatal diseases around the world. However, the mechanism of the development of gastric cancer is still not clarified. In addition, the anticancer drugs have cytotoxicity with different degrees. AnnexinA5, a member of the annexin family, has a great binding ability with the membrane phospholipid in a calcium dependent manner and is involved in the development of various cancers. This study aims to explore the influence of annexinA5 on human gastric cancer cells and whether it has the potential to be an auxiliary treatment to gastric cancer. In this study, the role of annexinA5 was detected from both the endogenous and the exogenous aspects on the gastric cancer cell lines MGC-803 and MKN-45. The cells were divided into a knockdown group in which RNA interference technique was used to suppress annexinA5 expression and a protein-supplementing group in which annexinA5 protein was added in the culture supernatant. After the suppression ratio of RNA interference was determined and the IC50 of annexinA5 protein was decided respectively, the cells’ proliferation was detected by MTT assay, colony formation assay, and the expression of PCNA. FCM assay and PI staining methods were applied to test cell apoptosis and necrosis. To investigate whether ANXA5 influence cell metastasis, wound healing assay and transwell assay were employed. To further detect the mechanism of annexinA5 action, the signal pathway was examined with Western Blot method. When ANXA5 gene was knocked down, cell proliferation and metastasis were promoted, while cell apoptosis was suppressed. On the other hand, after the annexinA5 protein was applied to the gastric cancer cells, cell proliferation and metastasis were inhibited, while cell apoptosis and necrosis were promoted. AnnexinA5 played its role via ERK signal pathway. ANXA5 acted as tumor suppressor gene in the gastric cancer by suppressing ERK signal pathway and has the potentiality to be an auxiliary anticancer agent.

Anti-cancer activity of anti-p185HER-2ricin A chain immunotoxin on gastric cancer cells

2010 ◽  
Vol 25 (7) ◽  
pp. 1266-1275 ◽  
Author(s):  
Xin-Xin Zhou ◽  
Feng Ji ◽  
Jing-Li Zhao ◽  
Lin-Fang Cheng ◽  
Cheng-Fu Xu
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Gastric Cancer Cells ◽  
Anti Cancer ◽  
A Chain ◽  
Cancer Activity

Quercetin induced cell apoptosis and altered gene expression in AGS human gastric cancer cells

2018 ◽  
Vol 33 (11) ◽  
pp. 1168-1181 ◽  
Author(s):  
Hung-Sheng Shang ◽  
Hsu-Feng Lu ◽  
Ching-Hsiao Lee ◽  
Han-Sun Chiang ◽  
Yung-Lin Chu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Altered Gene Expression ◽  
Altered Gene

scholarly journals Dihydromyricetin induces cell apoptosis via a p53-related pathway in AGS human gastric cancer cells

2015 ◽  
Vol 14 (4) ◽  
pp. 15564-15571 ◽  
Author(s):  
F.J. Ji ◽  
X.F. Tian ◽  
X.W. Liu ◽  
L.B. Fu ◽  
Y.Y. Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Related Pathway

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.

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