Selective p300 inhibitor C646 inhibited HPV E6-E7 genes, altered glucose metabolism and induced apoptosis in cervical cancer cells

2017 ◽  
Vol 812 ◽  
pp. 206-215 ◽  
Author(s):  
Hongpeng He ◽  
Yongwei Lai ◽  
Yunpeng Hao ◽  
Yupeng Liu ◽  
Zijiang Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Hpv E6 ◽  
Altered Glucose ◽  
Cervical Cancer Cells ◽  
Induced Apoptosis

scholarly journals Hsp90 Inhibitor SNX-2112 Enhances TRAIL-Induced Apoptosis of Human Cervical Cancer Cells via the ROS-Mediated JNK-p53-Autophagy-DR5 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-26
Author(s):  
Liubing Hu ◽  
Yan Wang ◽  
Zui Chen ◽  
Liangshun Fu ◽  
Sheng Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Hela Cells ◽  
Cell Apoptosis ◽  
Hsp90 Inhibitor ◽  
Cervical Cancer Cells ◽  
Ros Scavenger ◽  
Induced Apoptosis ◽  
Human Cervical Cancer

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent cancer cell apoptosis-inducing factor that can induce apoptosis in a variety of cancer cells. However, resistance to TRAIL in cancer cells is a huge obstacle in creating effective TRAIL-targeted clinical therapies. Thus, agents that can either enhance the effect of TRAIL or overcome its resistance are needed. In this study, we combined TRAIL with SNX-2112, an Hsp90 inhibitor we previously developed, to explore the effect and mechanism that SNX-2112 enhanced TRAIL-induced apoptosis in cervical cancer cells. Our results showed that SNX-2112 markedly enhanced TRAIL-induced cytotoxicity in HeLa cells, and this combination was found to be synergistic. Additionally, we found that SNX-2112 sensitized TRAIL-mediated apoptosis caspase-dependently in TRAIL-resistant HeLa cells. Mechanismly, SNX-2112 downregulated antiapoptosis proteins, including Bcl-2, Bcl-XL, and FLIP, promoted the accumulation of reactive oxygen species (ROS), and increased the expression levels of p-JNK and p53. ROS scavenger NAC rescued SNX-2112/TRAIL-induced apoptosis and suppressed SNX-2112-induced p-JNK and p53. Moreover, SNX-2112 induced the upregulation of death-receptor DR5 in HeLa cells. The silencing of DR5 by siRNA significantly decreased cell apoptosis by the combined effect of SNX-2112 and TRAIL. In addition, SNX-2112 inhibited the Akt/mTOR signaling pathway and induced autophagy in HeLa cells. The blockage of autophagy by bafilomycin A1 or Atg7 siRNA abolished SNX-2112-induced upregulation of DR5. Meanwhile, ROS scavenger NAC, JNK inhibitor SP600125, and p53 inhibitor PFTα were used to verify that autophagy-mediated upregulation of DR5 was regulated by the SNX-2112-stimulated activation of the ROS-JNK-p53 signaling pathway. Thus, the combination of SNX-2112 and TRAIL may provide a novel strategy for the treatment of human cervical cancer by overcoming cellular mechanisms of apoptosis resistance.

Benzobijuglone, a novel cytotoxic compound from Juglans mandshurica, induced apoptosis in HeLa cervical cancer cells

Phytomedicine ◽  
2007 ◽  
Vol 14 (12) ◽  
pp. 846-852 ◽  
Author(s):  
Zhi-Bo Li ◽  
Jing-Yun Wang ◽  
Bo Jiang ◽  
Xiu-Li Zhang ◽  
Li-Jia An ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Juglans Mandshurica ◽  
Cytotoxic Compound ◽  
Cervical Cancer Cells ◽  
Induced Apoptosis

Inhibition of tumorigenicity of cervical cancer cells in nude mice by HPV e6-e7 anti-sense RNA

1992 ◽  
Vol 51 (5) ◽  
pp. 831-834 ◽  
Author(s):  
Magnus von Knebel Doeberitz ◽  
Claudia Rittmüller ◽  
Harald Zur Hausen ◽  
Matthias dürst
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Nude Mice ◽  
Hpv E6 ◽  
Cervical Cancer Cells

Suppression of human 8-oxoguanine DNA glycosylase (OGG1) augments ultrasound-induced apoptosis in cervical cancer cells

Ultrasonics ◽  
2016 ◽  
Vol 72 ◽  
pp. 1-14
Author(s):  
Tao Xu ◽  
Yongli Nie ◽  
Jiao Bai ◽  
Linjun Li ◽  
Bo Yang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Dna Glycosylase ◽  
Cervical Cancer Cells ◽  
Induced Apoptosis

scholarly journals E6-mediated activation of JNK drives EGFR signalling to promote proliferation and viral oncoprotein expression in cervical cancer

2020 ◽  
Author(s):  
Ethan L. Morgan ◽  
James A. Scarth ◽  
Molly R. Patterson ◽  
Christopher W. Wasson ◽  
Georgia C. Hemingway ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Human Papillomaviruses ◽  
Signalling Pathway ◽  
Viral Oncoprotein ◽  
Hpv E6 ◽  
Cervical Cancer Cells ◽  
E6 And E7 ◽  
Novel Therapeutic

AbstractHuman papillomaviruses (HPV) are a major cause of malignancy worldwide, contributing to ~5% of all human cancers including almost all cases of cervical cancer and a growing number of ano-genital and oral cancers. HPV-induced malignancy is primarily driven by the viral oncogenes, E6 and E7, which manipulate host cellular pathways to increase cell proliferation and enhance cell survival, ultimately predisposing infected cells to malignant transformation. Consequently, a more detailed understanding of viral-host interactions in HPV-associated disease offers the potential to identify novel therapeutic targets. Here, we identify that the c-Jun N-terminal kinase (JNK) signalling pathway is activated in cervical disease and in cervical cancer. The HPV E6 oncogene induces JNK1/2 phosphorylation in a manner that requires the E6 PDZ binding motif. We show that blockade of JNK1/2 signalling using small molecule inhibitors, or knockdown of the canonical JNK substrate c-Jun, reduces cell proliferation and induces apoptosis in cervical cancer cells. We further demonstrate that this phenotype is at least partially driven by JNK-dependent activation of EGFR signalling via increased expression of EGFR and the EGFR ligands EGF and HB-EGF. JNK/c-Jun signalling promoted the invasive potential of cervical cancer cells and was required for the expression of the epithelial to mesenchymal transition (EMT)-associated transcription factor Slug and the mesenchymal marker Vimentin. Furthermore, JNK/c-Jun signalling is required for the constitutive expression of HPV E6 and E7, which are essential for cervical cancer cell growth and survival. Together, these data demonstrate a positive feedback loop between the EGFR signalling pathway and HPV E6/E7 expression, identifying a regulatory mechanism in which HPV drives EGFR signalling to promote proliferation, survival and EMT. Thus, our study has identified a novel therapeutic target that may be beneficial for the treatment of cervical cancer.

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