scholarly journals Role of NRF2 cascade in determining the differential response of cervical cancer cells to anticancer drugs- an in vitro study

2021 ◽  
Author(s):  
Pushkal Sinduvadi Ramesh ◽  
Sharanya Raja ◽  
Shwethambari Harave Udayakumar ◽  
Shruthi Chandrashekar ◽  
Suma M Nataraj ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Enzyme Activity ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Differential Response ◽  
Cancer Drugs ◽  
Nrf2 Pathway ◽  
Siha Cells ◽  
Anti Cancer ◽  
Cervical Cancer Cells

Abstract Background Cervical cancers are usually treatable if detected in early stages by a combination of therapies. However, the prognosis of cervical cancer patients with metastasis remains unfavorable due to the fact that most of the cervical carcinomas are either resistant to anticancer drugs or show signs of relapse after initial treatment. Therefore, it is important to control the chemoresistance as it is the key to develop effective treatment options for cervical cancer. Objective The current study aimed at evaluating the differential responses of cervical cancer cells to anti-cancer drugs and assessed whether the differences in the expression profiles of antioxidant genes regulated by NRF2 (nuclear factor erythroid-2-related factor 2), led to the variations in the sensitivities of the cancer cells to treatment. Methodology: Three cervical cancer cell lines were investigated for their differences in NRF2 pathway by measuring the gene expression and enzyme activity. The differences in the sensitivity to anti-cancer drugs and variation in ROS profile was also evaluated. The addition of exogenous drugs to manipulate the intracellular ROS and its effect on NRF2 pathway genes was also investigated. Results HeLa and SiHa cells were more sensitive to cisplatin and oxaliplatin treatment than C33A cells. HeLa and SiHa cells had significantly lower NRF2 gene levels, NQO1 enzyme activity and basal GSH levels than C33A cells. Levels of ROS induced were higher in HeLa than C33A cells. Conclusion Overall, the differences in the cellular levels of antioxidant regulatory genes led to the differential response of cervical cancer cells to anti-cancer drugs.

CRISPR-mediated knockdown of miR-214 modulates cell fate in response to anti-cancer drugs in HPV-negative and HPV-positive cervical cancer cells

2020 ◽  
Vol 45 (1) ◽  
Author(s):  
Prakriti Sen ◽  
Sayam Ghosal ◽  
Rudranil Hazra ◽  
Rimjhim Mohanty ◽  
Solomon Arega ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Fate ◽  
Cancer Drugs ◽  
Anti Cancer ◽  
Cervical Cancer Cells

scholarly journals Role of NRF2 cascade in determining the differential response of cervical cancer cells to anticancer drugs- an in vitro study

2021 ◽  
Author(s):  
Pushkal Sinduvadi Ramesh ◽  
Sharanya Raja ◽  
Shwethambari Harave Udayakumar ◽  
Shruthi Chandrashekar ◽  
Suma M Nataraj ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Expression Profiles ◽  
Differential Response ◽  
Related Factor ◽  
Aberrant Expression ◽  
Antioxidant Genes ◽  
Cervical Cancer Cells

Abstract The prognosis of cervical cancer patients with metastasis remains unfavorable due to the fact that most of the cervical carcinomas are either resistant to anticancer drugs or show signs of relapse after initial treatment. Therefore, it is important to control the chemoresistance as it is the key to develop effective treatment options. NRF2 (nuclear factor erythroid-2-related factor 2), a transcription factor whose aberrant expression is known to induce chemoresistance in various cancers was assessed in the study. It was evaluated whether the differences in the expression profiles of antioxidant genes regulated by NRF2 led to the variations in the sensitivities of the cervical cancer cells to cisplatin and oxaliplatin treatment. The variations in the ROS profile as well as the addition of exogenous drugs to manipulate the intracellular ROS and its effect on NRF2 pathway genes was also investigated. HeLa and SiHa cells which had significantly lower NRF2 gene levels, NQO1 enzyme activity and basal GSH levels than C33A cells were more sensitive to treatment. Levels of ROS induced were higher in HeLa than C33A cells. Overall, the differences in the cellular levels of antioxidant regulatory genes led to the differential response of cervical cancer cells to anti-cancer drugs.

scholarly journals Role of NRF2 cascade in determining the differential response of cervical cancer cells to anticancer drugs: an in vitro study

2021 ◽  
Author(s):  
Pushkal Sinduvadi Ramesh ◽  
Sharanya Raja ◽  
Shwethambari Harave Udayakumar ◽  
Shruthi Chandrashekar ◽  
Suma M. Nataraj ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
In Vitro Study ◽  
Differential Response ◽  
Vitro Study ◽  
Cervical Cancer Cells

The Antitumor Efficiency of Zinc Finger Nuclease Combined with Cisplatin and Trichostatin A in Cervical Cancer Cells

2020 ◽  
Vol 20 (17) ◽  
pp. 2125-2135
Author(s):  
Ci Ren ◽  
Chun Gao ◽  
Xiaomin Li ◽  
Jinfeng Xiong ◽  
Hui Shen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Zinc Finger ◽  
Hela Cells ◽  
Colony Formation ◽  
Trichostatin A ◽  
Combined Therapy ◽  
Hpv E7 ◽  
Anti Cancer ◽  
Cervical Cancer Cells

Background: Persistent infection with the high-risk of human papillomavirus (HR-HPVs) is the primary etiological factor of cervical cancer; HR-HPVs express oncoproteins E6 and E7, both of which play key roles in the progression of cervical carcinogenesis. Zinc Finger Nucleases (ZFNs) targeting HPV E7 induce specific shear of the E7 gene, weakening the malignant biological effects, hence showing great potential for clinical transformation. Objective: Our aim was to develop a new comprehensive therapy for better clinical application of ZFNs. We here explored the anti-cancer efficiency of HPV targeted ZFNs combined with a platinum-based antineoplastic drug Cisplatin (DDP) and an HDAC inhibitor Trichostatin A (TSA). Methods: SiHa and HeLa cells were exposed to different concentrations of DDP and TSA; the appropriate concentrations for the following experiments were screened according to cell apoptosis. Then cells were grouped for combined or separate treatments; apoptosis, cell viability and proliferation ability were measured by flow cytometry detection, CCK-8 assays and colony formation assays. The xenograft experiments were also performed to determine the anti-cancer effects of the combined therapy. In addition, the HPV E7 and RB1 expressions were measured by western blot analysis. Results: Results showed that the combined therapy induced about two times more apoptosis than that of ZFNs alone in SiHa and HeLa cells, and much more inhibition of cell viability than either of the separate treatment. The colony formation ability was inhibited more than 80% by the co-treatment, the protein expression of HPV16/18E7 was down regulated and that of RB1 was elevated. In addition, the xenografts experiment showed a synergistic effect between DDP and TSA together with ZFNs. Conclusion: Our results demonstrated that ZFNs combined with DDP or TSA functioned effectively in cervical cancer cells, and it provided novel ideas for the prevention and treatment of HPV-related cervical malignancies.

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 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 Mechanisms and Applications of the Anti-cancer Effect of Pharmacological Ascorbic Acid in Cervical Cancer Cells

2020 ◽  
Vol 10 ◽  
Author(s):  
Tsai-Ming Wu ◽  
Shu-Ting Liu ◽  
Ssu-Yu Chen ◽  
Gunng-Shinng Chen ◽  
Chia-Chun Wu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Ascorbic Acid ◽  
Cancer Cells ◽  
Anti Cancer ◽  
Cervical Cancer Cells

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.

scholarly journals Intracellular delivery of NF-κB small interfering RNA for modulating therapeutic activities of classical anti-cancer drugs in human cervical cancer cells

2013 ◽  
Vol 3 (1) ◽  
pp. 7 ◽  
Author(s):  
Anthony Stanislaus ◽  
Anil Philip Kunnath ◽  
Snigdha Tiash ◽  
Tahereh Fatemian ◽  
Nur Izyani Kamaruzman ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Intracellular Delivery ◽  
Cyclin B1 ◽  
Carbonate Apatite ◽  
Cancer Drugs ◽  
Small Interfering Rnas ◽  
Strong Electrostatic Interaction ◽  
Anti Cancer ◽  
Gene Transcripts

Cervical cancer is the second most common cancer and fourth leading cause of cancer-related deaths among women. Advanced stage of the disease is treated with radiation therapy and chemotherapy with poor therapeutic outcome and adverse side effects. NFκB, a well-known transcription factor in the control of immunity and inflammation, has recently emerged as a key regulator of cell survival through induction of antiapoptotic genes. Many human cancers, including cervical carcinoma, constitutively express NF-κB and a blockade in expression of its subunit proteins through targeted knockdown of the gene transcripts with small interfering RNAs (siRNA) could be an attractive approach in order to sensitize the cancer cells towards the widely used anti-cancer drugs. However, the inefficiency of the naked siRNA to cross the plasma membrane and its sensitiveness to nuclease-mediated degradation are the major challenges limiting the siRNA technology in therapeutic intervention. pH-sensitive carbonate apatite has been established as an efficient nano-carrier for intracellular delivery of siRNA, due to its strong electrostatic interaction with the siRNA, the desirable size distribution of the resulting siRNA complex for effective endocytosis and the ability of the endocytosed siRNA to be released from the degradable particles and escape the endosomes, thus leading to the effective knockdown of the target gene of cyclin B1 or ABCB1. Here, we report that carbonate apatite-facilitated delivery of the siRNA targeting NF-κB1 and NF-κB2 gene transcripts in HeLa, a human cervical adenocar- cinoma cell line expressing NF-κB, led to a synergistic effect in enhancement of chemosensitivity to doxorubicin, but apparently not to cisplatin or paclitaxel.

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