scholarly journals Cellular Levels of Oxidative Stress Affect the Response of Cervical Cancer Cells to Chemotherapeutic Agents

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Maria Filippova ◽  
Valery Filippov ◽  
Vonetta M. Williams ◽  
Kangling Zhang ◽  
Anatolii Kokoza ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cervical Cancer ◽  
Cancer Cells ◽  
Adaptive Systems ◽  
Chemotherapeutic Agents ◽  
Rt Pcr ◽  
Cellular Models ◽  
Siha Cells ◽  
Ros Metabolism ◽  
Cervical Cancer Cells

Treatment of advanced and relapsed cervical cancer is frequently ineffective, due in large part to chemoresistance. To examine the pathways responsible, we employed the cervical carcinoma-derived SiHa and CaSki cells as cellular models of resistance and sensitivity, respectively, to treatment with chemotherapeutic agents, doxorubicin, and cisplatin. We compared the proteomic profiles of SiHa and CaSki cells and identified pathways with the potential to contribute to the differential response. We then extended these findings by comparing the expression level of genes involved in reactive oxygen species (ROS) metabolism through the use of a RT-PCR array. The analyses demonstrated that the resistant SiHa cells expressed higher levels of antioxidant enzymes. Decreasing or increasing oxidative stress led to protection or sensitization, respectively, in both cell lines, supporting the idea that cellular levels of oxidative stress affect responsiveness to treatment. Interestingly, doxorubicin and cisplatin induced different profiles of ROS, and these differences appear to contribute to the sensitivity to treatment displayed by cervical cancer cells. Overall, our findings demonstrate that cervical cancer cells display variable profiles with respect to their redox-generating and -adaptive systems, and that these different profiles have the potential to contribute to their responses to treatments with chemotherapy.

scholarly journals MicroRNA-96-5p Facilitates the Viability, Migration, and Invasion and Suppresses the Apoptosis of Cervical Cancer Cells byNegatively Modulating SFRP4

2020 ◽  
Vol 19 ◽  
pp. 153303382093413 ◽  
Author(s):  
Huiling Zhang ◽  
Ruxin Chen ◽  
Jinyan Shao
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Clinical Stage ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Related Protein ◽  
Siha Cells ◽  
Gene Assay ◽  
Cervical Cancer Cells ◽  
Cancer Tissues

Purpose: The current study was intended to research the functional role and regulatory mechanism of microRNA-96-5p in the progression of cervical cancer. Methods: MicroRNA-96-5p expression in cervical cancer tissues was assessed by quantitative real-time polymerase chain reaction. The association between microRNA-96-5p expression and clinicopathological features of patients with cervical cancer was analyzed. MTT, flow cytometry, wound healing, and transwell assay were performed to evaluate the viability, apoptosis, migration, and invasion of Hela and SiHa cells. Targetscan, dual-luciferase reporter gene assay, and RNA pull-down analysis were constructed to evaluate the target relationship between microRNA-96-5p and secreted frizzled-related protein 4. Results: MicroRNA-96-5p was overexpressed in cervical cancer tissues, and microRNA-96-5p expression was markedly associated with the clinical stage and lymph node metastasis of patients with cervical cancer. Overexpressed microRNA-96-5p facilitated the viability, migration, invasion, and inhibited the apoptosis of Hela and SiHa cells, whereas suppression of microRNA-96-5p exerted the opposite trend. Secreted frizzled-related protein 4 was proved to be a target of microRNA-96-5p. Silencing of secreted frizzled-related protein 4 eliminated the anti-tumor effect of microRNA-96-5p on cervical cancer cells. Conclusions: MicroRNA-96-5p facilitated the viability, migration, and invasion and inhibited the apoptosis of cervical cancer cells via negatively regulating secreted frizzled-related protein 4.

scholarly journals Recombinant heat shock protein 27 (HSP27/HSPB1) protects against cadmium-induced oxidative stress and toxicity in human cervical cancer cells

2017 ◽  
Vol 22 (3) ◽  
pp. 357-369 ◽  
Author(s):  
Daiana G. Alvarez-Olmedo ◽  
Veronica S. Biaggio ◽  
Geremy A. Koumbadinga ◽  
Nidia N. Gómez ◽  
Chunhua Shi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cervical Cancer ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cancer Cells ◽  
Heat Shock Protein 27 ◽  
Cervical Cancer Cells ◽  
Human Cervical Cancer Cells ◽  
Human 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.

Calcitriol increases Dicer expression and modifies the microRNAs signature in SiHa cervical cancer cells

2015 ◽  
Vol 93 (4) ◽  
pp. 376-384 ◽  
Author(s):  
Ramiro José González-Duarte ◽  
Verna Cázares-Ordoñez ◽  
Sandra Romero-Córdoba ◽  
Lorenza Díaz ◽  
Víctor Ortíz ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Vitamin D ◽  
Cancer Cells ◽  
Cancer Biology ◽  
Response Element ◽  
Cancer Pathways ◽  
Siha Cells ◽  
Cervical Cancer Cells ◽  
Dicer Expression

MicroRNAs play important roles in cancer biology. Calcitriol, the hormonal form of vitamin D3, regulates microRNAs expression in tumor cells. In the present study we asked if calcitriol would modify some of the components of the microRNA processing machinery, namely, Drosha and Dicer, in calcitriol-responsive cervical cancer cells. We found that calcitriol treatment did not affect Drosha mRNA; however, it significantly increased Dicer mRNA and protein expression in VDR-positive SiHa and HeLa cells. In VDR-negative C33-A cells, calcitriol had no effect on Dicer mRNA. We also found a vitamin D response element in Dicer promoter that interacts in vitro to vitamin D and retinoid X receptors. To explore the biological plausibility of these results, we asked if calcitriol alters the microRNA expression profile in SiHa cells. Our results revealed that calcitriol regulates the expression of a subset of microRNAs with potential regulatory functions in cancer pathways, such as miR-22, miR-296-3p, and miR-498, which exert tumor-suppressive effects. In summary, the data indicate that in SiHa cells, calcitriol stimulates the expression of Dicer possibly through the vitamin D response element located in its promoter. This may explain the calcitriol-dependent modulation of microRNAs whose target mRNAs are related to anticancer pathways, further adding to the various anticancer mechanisms of calcitriol.

scholarly journals Up-regulation of peroxiredoxin 3 by high-risk human papillomavirus in cervical cancer cells

2021 ◽  
Author(s):  
Hou-Li Liu ◽  
Xiao-Juan Sun ◽  
Xiaoyan Li ◽  
Jingmin Li ◽  
Xianyong Bai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cervical Cancer Cells ◽  
Cancer Tissues ◽  
High Risk Hpv ◽  
Peroxiredoxin 3

IntroductionPeroxiredoxin 3 (PRX3) is a member of PRX family with antioxidant functions by scavenging hydrogen peroxide. Since the development of cervical cancer is causally linked to high-risk human papillomavirus (HPV) that induces oxidative stress, we conducted the present study to investigate the response of PRX3 to high-risk HPV infection.Material and methodsThis study included fifty-six patients with invasive squamous cervical cancer and sixty control patients with hysteromyoma. Enzyme-linked immunosorbent assay was performed to detect cervical oxidative stress and serum PRX3. The expression of PRX3 and oncoprotein E6 of HPV16 or HPV18 was examined in cervical cancer tissues by immunohistochemistry. Western Blot was applied to detect the expression of PRX3 and E6 in cervical cancer cell lines including CaSki, HeLa, and C33A.ResultsPatients with cervical cancer showed higher serum PRX3 than control patients with hysteromyoma. Levels of oxidative markers in cervical cancer tissues were elevated as compared to normal cervical epithelia. PRX3 expression was upregulated in cervical cancer tissues and the upregulation was positively associated with the expression of E6 of HPV16 or HPV18. The association was confirmed in HPV-containing cervical cancer cell lines including CaSki and HeLa.ConclusionsOur results indicated a positive response of PRX3 to HPV-induced oxidative stress. Serum PRX3 might be a potential indicator of active amplification of high-risk HPV in cervical cancer cells.

scholarly journals The degradation of Rap1GAP via E6AP-mediated ubiquitin-proteasome pathway is associated with HPV16/18-infection in cervical cancer cells

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yinghui Wang ◽  
Yihang Xie ◽  
Boxuan Sun ◽  
Yuwei Guo ◽  
Ling Song ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Suppressor Gene ◽  
Hpv Infection ◽  
Degradation Pathway ◽  
Human Papillomaviruses ◽  
Siha Cells ◽  
Cervical Cancer Cells ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Abstract Background Cervical cancers are closely associated with persistent high-risk human papillomaviruses (HR HPV) infection. The main mechanism involves the targeting of tumor suppressors, such as p53 and pRB, for degradation by HR HPV-encoded oncoproteins, thereby leading to tumorigenesis. Rap1GAP, a tumor suppressor gene, is down-regulated in many cancers. Previous studies have revealed that down-regulation of Rap1GAP is correlated with HPV16/18 infection in cervical cancer. However, the molecular mechanism remains unclear. In this study, we aimed to address the degradation pathway of Rap1GAP in HPV-positive cervical cancer cells. Methods HPV-positive (HeLa and SiHa) and negative (C33A) cervical cancer cells were used to analyze the pathways of Rap1GAP degradation. MG132 (carbobenzoxy-leucyl-leucyl-leucine) was used to inhibit protein degradation by proteasome. Co-immunoprecipitation (co-IP) was used to detect the interaction between Rap1GAP and E6AP. siRNA for E6AP was used to silence the expression of E6AP. Rapamycin was used to induce cell autophagy. Western blotting was used to check the levels of proteins. Results Following treatment with MG132, the levels of Rap1GAP were increased in the HR HPV-positive HeLa and SiHa cells, but not in the HPV-negative C33A cells. Co-immunoprecipitation assay revealed ubiquitinated Rap1GAP protein in HeLa and SiHa cells, but not in C33A cells. E6-associated protein (E6AP) mediated the ubiquitination of Rap1GAP by binding to it in HeLa and SiHa cells, but not in C33A cells. However, the levels of Rap1GAP were decreased in HeLa and SiHa cells after knocking down E6AP by siRNA. Silencing of E6AP did not affect the levels of Rap1GAP in C33A cells. Autophagy marker p62 was decreased and LC3 II/LC3 I was increased after knocking down E6AP in HeLa cells, but not in C33A cells. The levels of Rap1GAP were decreased after treating the cells with rapamycin to induce cell autophagy in HeLa and C33A cells. Conclusion Rap1GAP may be degraded by autophagy in cervical cancer cells, but HPV infection can switch the degradation pathway from autophagy to E6AP-mediated ubiquitin-proteasome degradation. E6AP may be a key component of the switch.

scholarly journals Microsecond Pulse Electrical Stimulation Inhibit the Proliferation of Cervical Cancer Cells through the Ras-Raf-MAPK Pathway

2020 ◽  
Author(s):  
Xiaoyue Xu ◽  
Shiyan Wang ◽  
Tingting Cao ◽  
Bing Xie ◽  
Xiuli Sun ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Electrical Stimulation ◽  
Pelvic Floor ◽  
Cancer Cells ◽  
Hela Cells ◽  
Mapk Pathway ◽  
Cell Counting ◽  
Proliferation Inhibition ◽  
Siha Cells ◽  
Cervical Cancer Cells

Abstract Objective: Using microsecond pulsed electrical stimulation (μsPES) applied to treat pelvic floor dysfunctions(PFDs) to stimulate the cervical cancer cells. To explore the effects and mechanisms of different μsPES on the proliferation of cervical cancer cells. Methods: Scheme #1 (1/4/1 Hz, 270/230/270 μs, 30min), scheme #2 (30 Hz, 500 μs, 20min), and scheme #3 (50 Hz, 250 μs, 20min) were selected from a pelvic floor rehabilitation therapy instrument. Three μsPES-based schemes each at 20, 40, 60, 80, and 100 mA current values were used to stimulate SiHa cells and HeLa cells. Cell counting kit-8 (CCK-8) assay was used to detect cell proliferation. Scheme #2 at 100 mA current was employed to stimulate SiHa cells and HeLa cells and then western blotting was applied to detect the expressions of the Ras-Raf-MAPK pathway. Results: Current with higer frequency and current intensity tended to have a more proliferation inhibition on cervical cancer cells. μsPES had a stronger proliferation inhibition in SiHa cells than HeLa cells. The expressions of MAPK, MEK1/2 and p-MEK1/2, Raf and p-Raf, Ras protein were significantly decreased in SiHa cells and HeLa cells compared with the control. The p-MAPK was up-regulated in HeLa cells while down-regulated in SiHa cells. Conclusions: μsPES could inhibit the proliferation of cervical cancer cells by suppressing the Ras-Raf-MAPK pathway. The μsPES applied for functional rehabilitation of pelvic floor nerves and muscles is safe for cervical cancer patients at the cellular level

scholarly journals Extracellular Vesicles from Human Papilloma Virus-Infected Cervical Cancer Cells Enhance HIV-1 Replication in Differentiated U1 Cell Line

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 239 ◽  
Author(s):  
Sabina Ranjit ◽  
Sunitha Kodidela ◽  
Namita Sinha ◽  
Subhash Chauhan ◽  
Santosh Kumar
Keyword(s):  
Oxidative Stress ◽  
Cervical Cancer ◽  
Human Papilloma Virus ◽  
Cancer Cells ◽  
Cell Line ◽  
Extracellular Vesicles ◽  
Papilloma Virus ◽  
Cervical Cancer Cells ◽  
Hpv Oncoproteins ◽  
Hiv 1

In the current study, we hypothesized that extracellular vesicles (EVs) secreted from human papilloma virus (HPV)-infected cervical cancer cells exacerbate human immunodeficiency virus (HIV)-1 replication in differentiated U1 cell line through an oxidative stress pathway. To test the hypothesis, we treated an HIV-1-infected macrophage cell line (U1) with HPV-infected Caski cell culture supernatant (CCS). We observed a significant increase in HIV-1 replication, which was associated with an increase in the expression of cytochrome P450 (CYPs 1A1 and 2A6) in the CCS-treated U1 cells. Furthermore, we isolated EVs from CCS (CCS-EVs), which showed the presence of CYPs (1A1, 2A6), superoxide dismutase 1 (SOD1), and HPV oncoproteins HPV16 E6. CCS-EVs when exposed to the U1 cells also significantly increased HIV-1 replication. Treatment of antioxidant, CYP1A1 and CYP2A6 inhibitors, and chemodietary agents with antioxidant properties significantly reduced the CCS and CCS-EVs mediated HIV-1 replication in U1 cells. Altogether, we demonstrate that cervical cancer cells exacerbate HIV-1 replication in differentiated U1 cell line via transferring CYPs and HPV oncoproteins through EVs. We also show that the viral replication occurs via CYP and oxidative stress pathways, and the viral replication is also reduced by chemodietary agents. This study provides important information regarding biological interactions between HPV and HIV-1 via EVs leading to enhanced HIV-1 replication.

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