scholarly journals Sine Oculis Homeobox Homolog 1 Regulates Mitochondrial Apoptosis Pathway Via Caspase-7 In Gastric Cancer Cells

2017 ◽  
Vol 8 (4) ◽  
pp. 636-645 ◽  
Author(s):  
Peizhun Du ◽  
Jing Zhao ◽  
Jing Wang ◽  
Yongchao Liu ◽  
Hong Ren ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Mitochondrial Apoptosis ◽  
Gastric Cancer Cells ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Sine Oculis ◽  
Caspase 7

scholarly journals Combination of Sodium Selenite and Doxorubicin Prodrug Ac-Phe-Lys-PABC-ADM Affects Gastric Cancer Cell Apoptosis in Xenografted Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Bo Wu ◽  
Jian Ge ◽  
Zixiong Zhang ◽  
Chuying Huang ◽  
Xiaodan Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Sodium Selenite ◽  
Combined Treatment ◽  
Xenograft Model ◽  
Tumor Xenograft ◽  
Mitochondrial Apoptosis ◽  
Gastric Cancer Cells ◽  
Apoptosis Pathway

The incidence of gastric cancer is extremely high in China, prompting the development of effective therapeutic strategies. Sodium selenite (SS) affects the proliferation and redifferentiation of gastric cancer cells and the Adriamycin prodrug Ac-Phe-Lys-PABC-ADM (PADM) reduces toxicity in gastric cancer treatment. However, the mechanisms involved therein remain unclear. In this study, nude mice were transplanted with SGC-7901 gastric cancer cells to construct a tumor xenograft model. After administration of SS and PADM, tumor weight and size were reduced. In addition, the levels of alanine aminotransferase, aspartate transaminase, creatinine, and lactate dehydrogenase were decreased, indicating improved hepatic and renal function and inhibited cancer cell metabolism. Furthermore, combined treatment of SS and PADM downregulated the expression of cell cycle-related proteins (cyclin-dependent kinase 4, Ki67, cyclin E, and cyclin D1), elevated that of proapoptosis proteins (Bax, cleaved caspase-3, cleaved caspase-9, and P53), and upregulated that of mitochondrial apoptosis-associated proteins (apoptotic protease activating factor 1 and second mitochondria-derived activator of caspases). In conclusion, combined treatment of SS and PADM effectively promoted apoptosis in gastric cancer xenografts via the mitochondrial apoptosis pathway.

scholarly journals miR-494 Sensitizes Gastric Cancer Cells to TRAIL Treatment Through Downregulation of Survivin

2018 ◽  
Vol 51 (5) ◽  
pp. 2212-2223 ◽  
Author(s):  
Shuning Xu ◽  
Danyang Li ◽  
Tianyuan Li ◽  
Lei Qiao ◽  
Ke Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Pcr Analysis ◽  
Gastric Cancer Cells ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Reporter Assays ◽  
Trail Sensitivity

Background/Aims: TNF-related apoptosis-inducing ligand (TRAIL) is a novel and low-toxic anti-tumor drug used for various cancers. However, cancer cells usually develop mechanisms to acquire the resistance against TRAIL. Among these changes, dysregulation of microRNAs (miRNAs) usually occurs in cancer cells and is responsible for induction of drug resistance. Methods: Expression of miR-494 in gastric cancer tissues and cell lines was detected by quantitative reverse transcriptase real time PCR (qRT-PCR) analysis. Effect of miR-494 on regulating the TRAIL sensitivity to gastric cancer cell lines was evaluated by MTT assays. Bioinformatics and luciferase reporter assays were used to confirm the regulation of miR-494 on survivin. Mitochondrial apoptosis pathway in gastric cancer cells was tested by western blot and flow cytometry analysis. Results: Obvious downregulation of miR-494 was observed in gastric cancer cells. Furthermore, we found that expression profile of miR-494 was associated with TRAIL-sensitivity in gastric cancer. Enforced expression of miR-494 was found to sensitize the gastric cancer cells to TRAIL-induced cytotoxicity. Mechanically, Luciferase reporter assays proved that survivin was the target of miR-494 in gastric cancer cells. Enforced expression of miR-494 decreased the expression of survivin, and thus promoted the TRAIL-induced mitochondria collapse and apoptosis pathway. Conclusion: MiR-494/survivin axis represents a potential mechanism which is responsible for TRAIL resistance in gastric cancer cells. Increasing the miR-494 expression may serve as a novel therapeutic strategy to sensitize gastric cancer cells to TRAIL treatment.

scholarly journals Intracellular expression of arginine deiminase activates the mitochondrial apoptosis pathway by inhibiting cytosolic ferritin and inducing chromatin autophagy

2020 ◽  
Author(s):  
Qingyuan Feng ◽  
Xuzhao Bian ◽  
Xuan Liu ◽  
Ying Wang ◽  
Huiting Zhou ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Western Blotting ◽  
Mitochondrial Damage ◽  
Arginine Deiminase ◽  
Immunofluorescent Staining ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
P53 Expression ◽  
Mitochondrial Apoptosis Pathway

Abstract Background: Based on its low toxicity, arginine starvation therapy has the potential to cure malignant tumors that cannot be treated surgically. The Arginine deiminase (ADI) gene has been identified to be an ideal cancer-suppressor gene. ADI expressed in the cytosol displays higher oncolytic efficiency than ADI-PEG20 (Pegylated Arginine Deiminase by PEG 20,000). However, it is still unknown whether cytosolic ADI has the same mechanism of action as ADI-PEG20 or other underlying cellular mechanisms. Methods: The interactions of ADI with other protein factors were screened by yeast hybrids, and verified by co-immunoprecipitation and immunofluorescent staining. The effect of ADI inhibiting the ferritin light-chain domain (FTL) in mitochondrial damage was evaluated by site-directed mutation and flow cytometry. Control of the mitochondrial apoptosis pathway was analyzed by Western Blotting and real-time PCR experiments. The effect of p53 expression on cancer cells death was assessed by siTP53 transfection. Chromatin autophagy was explored by immunofluorescent staining and Western Blotting. Results: ADI expressed in the cytosol inhibited the activity of cytosolic ferritin by interacting with FTL. The inactive mutant of ADI still induced apoptosis in certain cell lines of ASS- through mitochondrial damage. Arginine starvation also generated an increase in the expression of p53 and p53AIP1, which aggravated the cellular mitochondrial damage. Chromatin autophagy appeared at a later stage of arginine starvation. DNA damage occurred along with the entire arginine starvation process. Histone 3 (H3) was found in autophagosomes, which implies that cancer cells attempted to utilize the arginine present in histones to survive during arginine starvation. Conclusions: Mitochondrial damage is the major mechanism of cell death induced by cytosolic ADI. The process of chromatophagy does not only stimulate cancer cells to utilize histone arginine but also speeds up cancer cell death at a later stage of arginine starvation.

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