scholarly journals Anthocyanins fromVitis coignetiaePulliat Inhibit Cancer Invasion and Epithelial-Mesenchymal Transition, but These Effects Can Be Attenuated by Tumor Necrosis Factor in Human Uterine Cervical Cancer HeLa Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Jing Nan Lu ◽  
Won Sup Lee ◽  
Jeong Won Yun ◽  
Min Jeong Kim ◽  
Hye Jung Kim ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Hela Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Uterine Cervical Cancer ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Anticancer Effects ◽  
Dose Dependent ◽  
Necrosis Factor

Recently we have demonstrated that anthocyanins from fruits ofVitis coignetiaePulliat (AIMs) have anticancer effects. Here, we investigate the effects of AIMs on cell proliferation and invasion as well as epithelial-mesenchymal transition (EMT) which have been linked to cancer metastasis in human uterine cervical cancer HeLa cells. AIMs inhibited the invasion of HeLa cells in a dose-dependent manner. AIMs inhibited MMP-9 expression in a dose-dependent manner. AIMs inhibited the motility of HeLa cells in a wound healing test. AIMs still suppressed NF-κB activation induced by TNF. AIMs also inhibited EMT in HeLa cells. AIMs suppressed vimentin, N-cadherin, andβ-catenin expression and induced E-cadherin. AIMs also suppressed expression ofβ-catenin and Snail, which was regulated by GSK-3. These effects of AIMs were also limited in the HeLa cells treated with TNF. In conclusion, this study indicates that AIMs have anticancer effects by suppressing NF-κB-regulated genes and EMT, which relates to suppression of IκBαphosphorylation and GSK-3 activity, respectively. However, the effects of AIMs were attenuated in the TNF-high condition.

scholarly journals Baicalein Inhibits the Proliferation of Cervical Cancer Cells Through the GSK3β-Dependent Pathway

2018 ◽  
Vol 26 (4) ◽  
pp. 645-653 ◽  
Author(s):  
Xiaoling Wu ◽  
Zhiqin Yang ◽  
Huimin Dang ◽  
Huixia Peng ◽  
Zhijun Dai
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Hela Cells ◽  
Glycogen Synthase ◽  
Dependent Manner ◽  
Cervical Cancer Cells ◽  
Dose Dependent ◽  
Dependent Pathway

Baicalein, a flavonoid derived from the root of Scutellaria baicalensis, has been reported to possess multiple pharmacological activities, such as anticancer and anti-inflammatory properties. This study investigated the effect of baicalein in cervical cancer cells. Cell growth curve and MTT assay were performed and revealed that baicalein inhibited the proliferation of SiHa and HeLa cells in a dose-dependent manner. We further found that baicalein arrested the cell cycle of SiHa and HeLa cells at the G0/G1 phase by suppressing the expression of cyclin D1 through the downregulation of phosphorylated protein kinase B (p-AKT) and phosphorylated glycogen synthase kinase 3β (p-GSK3β) according to FACS assays and Western blotting. Moreover, when CHIR-99021, a GSK3β inhibitor, was added to baicalein-treated SiHa cells, the expression of cyclin D1 was recovered, and cell proliferation was promoted. In conclusion, these data indicated that baicalein suspended the cell cycle at the G0/G1 phase via the downregulation of cyclin D1 through the AKT‐GSK3β signaling pathway and further inhibited the proliferation of SiHa and HeLa cervical cancer cells.

scholarly journals CD36 promotes the epithelial–mesenchymal transition and metastasis in cervical cancer by interacting with TGF-β

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Min Deng ◽  
Xiaodong Cai ◽  
Ling Long ◽  
Linying Xie ◽  
Hongmei Ma ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Cd36 Expression ◽  
Cervical Cancer Cells

Abstract Background Accumulating evidence indicates that CD36 initiates metastasis and correlates with an unfavorable prognosis in cancers. However, there are few reports regarding the roles of CD36 in initiation and metastasis of cervical cancer. Methods Using immunohistochemistry, we analyzed 133 cervical cancer samples for CD36 protein expression levels, and then investigated the correlation between changes in its expression and clinicopathologic parameters. The effect of CD36 expression on the epithelial–mesenchymal transition (EMT) in cervical cancer cells was evaluated by Western immunoblotting analysis. In vitro invasion and in vivo metastasis assays were also used to evaluate the role of CD36 in cervical cancer metastasis. Results In the present study, we confirmed that CD36 was highly expressed in cervical cancer samples relative to normal cervical tissues. Moreover, overexpression of CD36 promoted invasiveness and metastasis of cervical cancer cells in vitro and in vivo, while CD36 knockdown suppressed proliferation, migration, and invasiveness. We demonstrated that TGF-β treatment attenuated E-cadherin expression and enhanced the expression levels of CD36, vimentin, slug, snail, and twist in si-SiHa, si-HeLa, and C33a–CD36 cells, suggesting that TGF-β synergized with CD36 on EMT via active CD36 expression. We also observed that the expression levels of TGF-β in si-SiHa cells and si-HeLa cells were down-regulated, whereas the expression levels of TGF-β were up-regulated in C33a–CD36 cells. These results imply that CD36 and TGF-β interact with each other to promote the EMT in cervical cancer. Conclusions Our findings suggest that CD36 is likely to be an effective target for guiding individualized clinical therapy of cervical cancer.

scholarly journals Potential Role of DEC1 in Cervical Cancer Cells Involving Overexpression and Apoptosis

2020 ◽  
Vol 2 (1) ◽  
pp. 26-38
Author(s):  
Fuyuki Sato ◽  
Ujjal K. Bhawal ◽  
Nao Sugiyama ◽  
Shoko Osaki ◽  
Kosuke Oikawa ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Hela Cells ◽  
Epithelial Mesenchymal Transition ◽  
Stem Cell Markers ◽  
Mesenchymal Transition ◽  
Helix Loop Helix ◽  
Siha Cells ◽  
Cervical Cancer Cells ◽  
Human Cervical Cancer

Basic helix-loop-helix (BHLH) transcription factors differentiated embryonic chondrocyte gene 1 (DEC1) and gene 2 (DEC2) regulate circadian rhythms, apoptosis, epithelial mesenchymal transition (EMT), invasions and metastases in various kinds of cancer. The stem cell markers SOX2 and c-MYC are involved in the regulation of apoptosis and poor prognosis. In cervical cancer, however, their roles are not well elucidated yet. To determine the function of these genes in human cervical cancer, we examined the expression of DEC1, DEC2, SOX2 and c-MYC in human cervical cancer tissues. In immunohistochemistry, they were strongly expressed in cancer cells compared with in non-cancerous cells. Notably, the strong rate of DEC1 and SOX2 expressions were over 80% among 20 cases. We further examined the roles of DEC1 and DEC2 in apoptosis. Human cervical cancer HeLa and SiHa cells were treated with cisplatin—HeLa cells were sensitive to apoptosis, but SiHa cells were resistant. DEC1 expression decreased in the cisplatin-treated HeLa cells, but had little effect on SiHa cells. Combination treatment of DEC1 overexpression and cisplatin inhibited apoptosis and affected SOX2 and c-MYC expressions in HeLa cells. Meanwhile, DEC2 overexpression had little effect on apoptosis and on SOX2 and c-MYC expressions. We conclude that DEC1 has anti-apoptotic effects and regulates SOX2 and c-MYC expressions on apoptosis.

A Comprehensive Review on Crosstalk of Human Papilloma Virus oncoproteins and developmental/self-renewal pathways during the pathogenesis of uterine cervical cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Afza Ahmad ◽  
Irfan Ahmad Ansari
Keyword(s):  
Cervical Cancer ◽  
Human Papilloma Virus ◽  
Epithelial Mesenchymal Transition ◽  
Wnt Signaling Pathway ◽  
Hpv Infection ◽  
Uterine Cervical Cancer ◽  
Self Renewal ◽  
Papilloma Virus ◽  
Mesenchymal Transition ◽  
E6 And E7

: Cervical cancer, a cancer arising from the uterine cervix has been regarded as the fourth most frequent gynecological malignancy among females worldwide. Epidemiological reports have shown that uterine cervical cancer is a global health issue among womens of specially developing countries and consequently creates an economic and medical burden in the society. The main causative agent of cervical carcinoma is high risk human papilloma virus (HPV 16 and HPV 18). Molecular studies have revealed the expression two viral genes E6 and E7 after HPV infection in the epithelial cells of cervix. These gene products are known to inactivate the major tumor suppressors, p53 and retinoblastoma protein (pRB), respectively. Moreover, the role of self-renewal pathways such as Hedgehog, Notch and Wnt has also been linked with drug resistance in cancer cells and epithelial mesenchymal transition during metastasis in pathogenesis of cervical cancer. Although, the mechanism of interaction of HPV E6 and E7 with each and every component of above described developmental pathways is not elucidated yet, but preliminary reports of their crosstalk have begun to emerge. Understanding the interplay between these oncoproteins and developmental/self-renewal pathways is highly important in terms of designing new and targeted therapeutic approach against cervical cancer. Hence, this review cynosure the carcinogenesis of HPV with the brief description of its virology and also establishes the crosstalk between oncoproteins E6 & E7 and Hedgehog, Notch and Wnt signaling pathway.

Proliferation Inhibition and Apoptosis Induction of Juglone on Human Cervical Cancer HeLa Cells

2014 ◽  
Vol 912-914 ◽  
pp. 1961-1964 ◽  
Author(s):  
Wei Zhang ◽  
Wen He Zhu ◽  
Yan Li ◽  
Jun Luo ◽  
Shi Jie Lv
Keyword(s):  
Cervical Cancer ◽  
Hela Cells ◽  
Control Group ◽  
Dependent Manner ◽  
Inverted Microscope ◽  
Cervical Cancer Cells ◽  
Human Cervical Cancer Cells ◽  
Dose Dependent ◽  
Human Cervical Cancer

Abstract: To investigate whether juglone could inhibits the proliferation on human cervical cancer cells (HeLa) in vitro. Cells were divided into control group, different concentration (10μM, 20μM, 50μM, 100μM and200μM) juglone groups for different durations. The viability of HeLa cells was detected by methyl thiazolyl tetrazolium (MTT) assay. The morphology changes of HeLa cells were observed by inverted microscope .The results showed that the viability of HeLa cells was decreased and the cell morphology was changed in a dose-dependent manner after treatment different concentration juglone for 24h when compared with control group. The results suggest that Juglone may be effective for the treatment of HeLa cells.

scholarly journals Identification and validation of putative target genes regulated by miR-34 in cervical cancer

2021 ◽  
Author(s):  
Nalini Venkatesan ◽  
Ashley Xavier ◽  
Sindhu K.J. ◽  
Himanshu Sinha ◽  
Karunagaran Devarajan
Keyword(s):  
Cervical Cancer ◽  
Candidate Genes ◽  
Large Scale ◽  
Cancer Metastasis ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Target Prediction ◽  
Functional Enrichment ◽  
Mesenchymal Transition ◽  
Putative Target

The emergence of large-scale transcriptomic data provides the opportunity for identifying novel putative targets of microRNAs (miRNAs). In this study, we followed a computational pipeline to predict the candidate gene targets of the miR-34 family. This approach integrates the expressions of miR-34 with genes of heterogeneous primary cervical epithelial squamous cell carcinomas (CESC). Integration of miR-34b and epithelial-mesenchymal transition (EMT) regulated genes has also been focussed, EMT being a reversible process that fuels cancer metastasis. An in-silico approach involving three processes was carried out with CESC datasets of the cancer atlas genome (TCGA), which includes correlation analysis, target prediction database lookup, functional enrichment, network analysis, survival analysis, and EMT score derivation. The results indicate that the miR-34 family may regulate the candidate genes of the mTOR pathway, cell cycle (CCND2) and cell adhesion functions (FZD4). Further, the study reveals the possible regulation of EMT signature genes, namely BMP7, CAV1 and ID2by miR-34b. Further, these transcriptomic signatures were validated in a subset of CESC from the South Asian Indian population (n = 10) and in non-cancerous cervical tissues (n = 5). Upon stably expressing miR-34b in cervical cancer cells (C33A and HeLa), we found repression of these candidate genes and a low negative correlation (r2 = 0.07) between miR-34b and EMT score indicating FN1 as its putative target. Together, these studies revealed the potential targets of the miR-34 family, especially miR-34b, with the hope that they would emerge as potential biomarkers and/or promising therapeutic targets in CESC.

scholarly journals Altered translation initiation ofGja1limits gap junction formation during epithelial–mesenchymal transition

2018 ◽  
Vol 29 (7) ◽  
pp. 797-808 ◽  
Author(s):  
Carissa C. James ◽  
Michael J. Zeitz ◽  
Patrick J. Calhoun ◽  
Samy Lamouille ◽  
James W. Smyth
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Translation Initiation ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Ectopic Expression ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Junction Protein ◽  
Junction Formation

Epithelial–mesenchymal transition (EMT) is activated during development, wound healing, and pathologies including fibrosis and cancer metastasis. Hallmarks of EMT are remodeling of intercellular junctions and adhesion proteins, including gap junctions. The GJA1 mRNA transcript encoding the gap junction protein connexin43 (Cx43) has been demonstrated to undergo internal translation initiation, yielding truncated isoforms that modulate gap junctions. The PI3K/Akt/mTOR pathway is central to translation regulation and is activated during EMT, leading us to hypothesize that altered translation initiation would contribute to gap junction loss. Using TGF-β–induced EMT as a model, we find reductions in Cx43 gap junctions despite increased transcription and stabilization of Cx43 protein. Biochemical experiments reveal suppression of the internally translated Cx43 isoform, GJA1-20k in a Smad3 and ERK-dependent manner. Ectopic expression of GJA1-20k does not halt EMT, but is sufficient to rescue gap junction formation. GJA1-20k localizes to the Golgi apparatus, and using superresolution localization microscopy we find retention of GJA1-43k at the Golgi in mesenchymal cells lacking GJA1-20k. NativePAGE demonstrates that levels of GJA1-20k regulate GJA1-43k hexamer oligomerization, a limiting step in Cx43 trafficking. These findings reveal alterations in translation initiation as an unexplored mechanism by which the cell regulates Cx43 gap junction formation during EMT.

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