scholarly journals Emodin Induced Necroptosis and Inhibited Glycolysis in the Renal Cancer Cells by Enhancing ROS

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Ke-jie Wang ◽  
Xiang-yu Meng ◽  
Jun-feng Chen ◽  
Kai-yun Wang ◽  
Cheng Zhou ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Signaling Pathway ◽  
Renal Cancer ◽  
Annexin V ◽  
Chinese Herbs ◽  
Dependent Manner ◽  
Cancer Cell Growth ◽  
Renal Cancer Cell ◽  
Significant Toxicity ◽  
Related Proteins

Renal cell carcinoma (RCC) is a tumor with unpredictable presentation and poor clinical outcome. RCC is always resistant to chemotherapy and radiation, and weakly sensitive to immunotherapeutic agents. Therefore, novel agents and approaches are urgently needed for the treatment of RCC. Emodin, an anthraquinone compound extracted from rhubarb and other traditional Chinese herbs, has been implicated in a wide variety of pharmacological effects, such as anti-inflammatory, antiviral, and antitumor activities. However, its role in RCC remains unknown. In this study, we found that emodin effectively killed renal cancer cells without significant toxicity to noncancerous cell HK-2. Flow cytometry assay with Annexin V-FITC and PI demonstrated that emodin induces necroptosis, but not apoptosis, in renal cancer cells. Meanwhile, the phosphorylation levels of RIP1 and MLKL, the key necroptosis-related proteins, were significantly increased. To explore how emodin inhibits kidney tumor growth, we tested reactive oxygen species (ROS) levels and found that the levels of ROS increased upon emodin treatment in a dose-dependent manner. Further studies demonstrated that emodin induces necroptosis through ROS-mediated activation of JNK signaling pathway and also inhibits glycolysis by downregulation of GLUT1 through ROS-mediated inactivation of the PI3K/AKT signaling pathway. Our findings revealed the potential mechanisms by which emodin suppresses renal cancer cell growth and will help develop novel therapeutic approaches for patients with JNK- or PI3K/AKT-dysregulated renal cancer.

scholarly journals Emodin induced necroptosis and inhibited glycolysis in the renal cancer cells by enhancing ROS

2020 ◽  
Author(s):  
Ke-jie Wang ◽  
Xiang-yu Meng ◽  
Jun-feng Chen ◽  
Kai-yun Wang ◽  
Cheng Zhou ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Flow Cytometry ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Renal Cancer ◽  
Reactive Oxygen ◽  
Chinese Herbs ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Flow Cytometry Assay

Abstract Background: Renal cell carcinoma (RCC) is a tumor with unpredictable presentation and poor clinical outcome. RCC is always resistant to chemotherapy, radiation, and weakly sensitive to immunotherapeutic agents. Therefore, novel agents and approaches are urgently needed for the treatment of RCC. Emodin, an anthraquinone compound extracted from rhubarb and other traditional Chinese herbs, has been implicated in a wide variety of pharmacological effects, such as anti-inflammatory, antiviral, and antitumor activities. However，its role in RCC remains unkown. Methods: Flow cytometry assay and lactate dehydrogenase release assay were used to detect the cell death. Reactive oxygen species was tested by the dye MitoSox and DCFH-DA. Glucose-6-phosphate, pyruvate and ATP level were measured to evaluate the glycolysis process. Western blot was used to detect protein expression. Results: Emodin effectively killed renal cancer cells without significant toxicity to normal renal tubular epithelial cell. Flow cytometry assay with Annexin V-FITC and PI demonstrated that emodin induces necroptosis, but not apoptosis, in renal cancer cells. Meanwhile, the phosphorylation levels of RIP1 and MLKL, the key necroptosis-related proteins, were significantly increased. To explore how emodin inhibits kidney tumor growth, reactive oxygen species (ROS) levels were tested and the levels of ROS increased upon emodin treatment in a dose-dependent manner. Further studies demonstrated that emodin induced necroptosis through ROS-mediated activation of JNK signaling pathway, and also inhibited glycolysis by down-regulation GLUT1 by ROS-mediated inactivation of PI3K/AKT signaling pathway. Conclusion: These findings revealed the potential mechanisms by which emodin suppresses renal cancer cell growth, and will help develop novel therapeutic approaches for patients with JNK- or PI3K/AKT-dysregulated renal cancer.

scholarly journals Inhibition of renal cancer cell growth by oncolytic adenovirus armed short hairpin RNA targeting hTERT gene

2009 ◽  
Vol 8 (1) ◽  
pp. 84-91 ◽  
Author(s):  
Jun-Nian Zheng ◽  
Dong-Sheng Pei ◽  
Fang-Hao Sun ◽  
Bao-Fu Zhang ◽  
Xin-Yuan Liu ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cell ◽  
Renal Cancer ◽  
Oncolytic Adenovirus ◽  
Cancer Cell Growth ◽  
Hairpin Rna ◽  
Htert Gene ◽  
Renal Cancer Cell ◽  
Rna Targeting ◽  
Short Hairpin

The Effect of Shikonin on U87 Cells Through Notch2 Signaling Pathway and Its Mechanism

2021 ◽  
Vol 11 (2) ◽  
pp. 290-294
Author(s):  
Lei Yuan ◽  
Ting Zhang ◽  
Hong Pan ◽  
Fei Wang
Keyword(s):  
Signaling Pathway ◽  
Protein Level ◽  
Theoretical Basis ◽  
Glioma Cells ◽  
Annexin V ◽  
Inhibitory Effect ◽  
Antioxidant Effect ◽  
Dependent Manner ◽  
Downstream Signaling ◽  
U87 Cells

Background: The paper explored the inhibitory effect of Shikonin on Notch2 signaling pathway of U87 cells and elucidated the mechanism. Material and methods: CCK-8 was used to determine the viability of U87 cells. The Kit was used to detect the levels of ROS and GSH in the cells. After Annexin V-FITC/PI staining, flow cytometry was used to detect the effect of Shikonin on U87 cell apoptosis. Western Blotting was used to detect the expressions of Notch2, Notch3, Hes1 and Hey1. The levels of NH4Cl and MG132 were determined to measure the effect of Shikonin inhibiting Notch2 protein level in U87 cells, and the effect of Shikonin on Itch inhibiting Notch2 protein level. Results: Shikonin can inhibit the expressions of Notch2 and Notch3 proteins and the levels of downstream signaling molecules Hes1 and Hey1 in U87 cells, and in a concentration- and time dependent manner. Shikonin can promote the degradation of Notch2 via the lysosomal pathway, which is associated with the up-regulation of the Itch expression. The inhibition of Notch2 and cell viability is related to the levels of GSH and ROS in cells, and Shikonin can down-regulate Notch2 to inhibit the proliferation of U87 cells. Conclusion: Shikonin inhibits the malignancy of glioma cells by promoting the degradation of Notch2 through the lysosomal pathway, which is related to the antioxidant effect. The results of our experiments provided certain experimental and theoretical basis for Shikonin treating glioma.

scholarly journals Epithelial–mesenchymal transition and metastasis of colon cancer cells induced by the FAK pathway in cancer-associated fibroblasts

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052093124
Author(s):  
Xuefeng Xuefeng ◽  
Ming-Xing Hou ◽  
Zhi-Wen Yang ◽  
Agudamu Agudamu ◽  
Feng Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
3D Culture ◽  
Cancer Associated Fibroblasts ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Lovo Cells ◽  
Related Proteins

Objective The role and mechanism of tetrathiomolybdate (TM) in cancer-associated fibroblasts (CAFs) in colon cancer using three-dimensional (3D) culture were investigated, and the associations between the focal adhesion kinase (FAK) pathway and epithelial–mesenchymal transition (EMT) in CAFs were explored. Methods A 3D co-culture model of colon cancer LOVO cells with CAFs and normal fibroblasts (NFs) was established using Matrigel as a scaffold material. The differential expression of LOXL2 (lysyl oxidase-like 2) in the supernatant of CAFs and NFs was determined using ELISA, and expression levels of EMT-related proteins and FAK signaling pathway-related proteins were determined using western blot. Results LOXL2 levels secreted by CAFs were higher compared with that secreted by NFs. In the CAF + LOVO group, compared with the LOVO group, E-cadherin expression decreased significantly, while N-cadherin and F-PAK expression increased significantly. TM results were opposite compared with the above results. Conclusions CAFs stimulate EMT in human colon cancer LOVO cells by secreting LOXL2 to activate the FAK signaling pathway, thereby promoting tumor metastasis. TM inhibited the occurrence of EMT in the CAF-induced colon cancer LOVO cell line, thereby reducing the invasion and metastasis of colon cancer cells.

scholarly journals Anticancer Potential of Fruit Extracts from Vatica diospyroides Symington Type SS and Their Effect on Program Cell Death of Cervical Cancer Cell Lines

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Atchara Chothiphirat ◽  
Kesara Nittayaboon ◽  
Kanyanatt Kanokwiroon ◽  
Theera Srisawat ◽  
Raphatphorn Navakanitworakul
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Morphological Changes ◽  
Annexin V ◽  
Siha Cell ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Cervical Cancer Cells ◽  
Dose Dependent

Vatica diospyroides Symington is locally known as Chan-Ka-Pho in Thailand. Ancient people have used it as therapeutic plant for cardiac and blood tonic cure. The purpose of this study was to investigate the potential cytotoxicity and selectivity of the extracts from V. diospyroides type SS fruit on cervical cancer HeLa and SiHa cell lines and to examine its underlying mechanism of action. MTT assay revealed that the extracts showed inhibition of cell survival in a dose-dependent manner and exhibited highly cytotoxic activity against both HeLa and SiHa cells with IC50 value less than 20 μg/mL along with less toxicity against L929 cells. Acetone cotyledon extract (ACE) showed the best selectivity index value of 4.47 (HeLa) and 3.51 (SiHa). Distinctive morphological changes were observed in ACE-treated cervical cancer cells contributing to apoptosis action. Flow cytometry analysis with Annexin V-FITC and PI staining precisely indicated that ACE induced apoptosis in HeLa and SiHa cell lines in a dose-dependent manner. Treatment of ACE with half IC50 caused DNA fragmentation and also activated increasing of bax and cleaved caspase-8 protein in HeLa cells after 48 h exposure. The results suggest that ACE has potent and selective cytotoxic effect against cervical cancer cells and the potential to induce bax and caspase-8-dependent apoptosis. Hence, the ACE could be further exploited as a potential lead in cancer treatment.

scholarly journals Hsp60 and IL-8 axis promotes apoptosis resistance in cancer

2019 ◽  
Vol 121 (11) ◽  
pp. 934-943 ◽  
Author(s):  
Sandeep Kumar ◽  
Jordan O’Malley ◽  
Ajay Kumar Chaudhary ◽  
Joseph R. Inigo ◽  
Neelu Yadav ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Combined Treatment ◽  
Annexin V ◽  
Underlying Mechanism ◽  
Competitive Inhibitor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Heat Shock Protein 60 ◽  
Apoptosis Resistance ◽  
Upstream Regulator

Abstract Background Interleukin-8 (IL-8) and heat shock protein 60 (Hsp60) play crucial roles in cell survival and maintenance of cellular homoeostasis. However, cross talks between these two proteins are not defined. Methods IL-8 expression in tumour tissue sections was analysed by immunohistochemistry. IL-8 expression and release in cancer cells was quantified using enzyme-linked immunosorbent assay (ELISA). Apoptosis was quantified using caspase activity and Annexin-V/PI staining. Results We observed IL-8 release from cancer cells in response to histone deacetylase inhibitor, apicidin (Api), and non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase, thapsigargin (TG). IL-8 release was increased upon TG-treatment. TG-induced IL-8 expression was reduced in the presence of Api in Bax-dependent manner. Increased apoptosis was associated with decreased IL-8 expression in response to combined treatment of TG and Api. TG and Api combination induced caspase-8 and caspase-9 dependent apoptosis. Hsp60 knockdown abrogated IL-8 expression induced by Api, TG, and their combination. The level of TGF-β, an upstream regulator of IL-8, was decreased upon Hsp60-silencing. Knocking down Hsp60 decreased IL-8 expression and its release in prostate cancer cell xenograft tumours in SCID mice. Conclusion This study describes the underlying mechanism associated with apoptosis resistance mediated via Hsp60-IL-8 axis in cancer.

scholarly journals UBE2S promotes the progression and Olaparib resistance of ovarian cancer through Wnt/β-catenin signaling pathway

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Wenjing Hu ◽  
Min Li ◽  
Youguo Chen ◽  
Xinxian Gu
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Cancer Proliferation ◽  
Skov3 Cells

Abstract Background Ovarian cancer is the most lethal gynecologic malignancy worldwide. Olaparib, an inhibitor of poly (ADP-ribose) polymerase (PARP), is becoming widely used in ovarian cancer treatment. The overall survival of ovarian cancer has not been significantly changed over the past decades and ovarian cancer has become increasingly resistant to the Olaparib. Ubiquitin-conjugating enzyme E2S (UBE2S) has been proved to promote malignant behaviors in many cancers. However, the function of UBE2S in the development and Olaparib resistance of ovarian cancer are unclear. Materials and methods In this study, we detected the expression of UBE2S in normal fallopian tube (FT) and HGSOC tissues. A2780 and SKOV3 cells were stably transfected with PCMV-UBE2S, PCMV-UBE2S-C95S, UBE2S shRNAs, and negative controls. The CCK8 assay and clonogenic assay were conducted to analyze ovarian cancer proliferation and Olaparib resistance. The transwell assay was performed to determine the migration and invasion of ovarian cancer cells. The relative protein levels of the Wnt/β-catenin signaling pathway were tested using western blot. The ovarian cancer cells were treated with XAV-939 to investigate the role of Wnt/β-catenin signaling pathway in Olaparib resistance. Moreover, we repeated some above procedures in the xenograft model. Results The results demonstrated that UBE2S was highly upregulated in HGSOC and that high UBE2S expression was correlated with poor outcomes in HGSOC. UBE2S promoted ovarian cancer proliferation and drived the migration and invasion of ovarian cancer cells. UBE2S activated the Wnt/β-catenin signaling pathway in ovarian cancer resulting in Olaparib resistance in vitro and in vivo. Furthermore, UBE2S enhanced the proliferation and Olaparib resistance of ovarian cancer in its enzymatic activity dependent manner. Conclusions These data suggest a possible molecular mechanism of proliferation and metastasis of ovarian cancer and highlight the potential role of UBE2S as a therapeutic target in ovarian cancer.

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