scholarly journals ANTICANCER EFFECTS OF RETINOIC ACID IN CERVICAL CANCER CELLS

2019 ◽  
Vol 81 (2) ◽  
Author(s):  
Sugania Malar Chinapayan ◽  
Praseetha Prabhakaran
Keyword(s):  
Cervical Cancer ◽  
Stem Cell ◽  
Retinoic Acid ◽  
Cell Viability ◽  
Cancer Cells ◽  
Hela Cells ◽  
Stem Cell Markers ◽  
Anticancer Effect ◽  
Cervical Cancer Cells ◽  
Differentiation Marker

Cervical cancer is a leading cause of cancer-related death in women, and it is known to have a poor prognosis. This is because, patients develop progressive or recurrent tumours after primary treatment, and the major reason for tumour recurrence is the presence of cancer stem cells (CSCs). It is known that retinoic acid (RA) has potential therapeutic effects on cervical cancer. However, the possible mode of action of RA in cervical cancer cells, and its relation to CSCs remains elusive. The aim of this research was to determine the anticancer effect of RA in cervical cancer cells (HeLa). HeLa cells were treated by various concentrations of RA ranging from 5-50µM to determine the effect of RA on cell viability, and cell proliferation. Both experiments were carried out using Celltiter-glo 2.0 assay and CyQuant NF assay, respectively. Apoptosis activity was determined using Caspase-Glo 3/7 assay. Immunofluorescent staining was conducted to detect the expression of differentiation marker (pan-keratin), and stem cell markers (CD133 and SSEA4) on untreated and treated HeLa cells with 10µM of RA. The findings showed that RA reduced cell viability and proliferation in a dose-dependent manner by 12-83% and 22-86%, respectively. However, a change in caspase3/7 activity between untreated, and 10µM RA-treated Hela cells were not detected indicating absence of apoptotic activity. The study also revealed that expression of differentiation marker (pan-keratin) was up-regulated, while expressions of stem cell markers (CD133 and SSEA4) were down-regulated. In addition, morphology of HeLa cells displayed a more differentiated phenotype that is less proliferative upon RA treatment. These findings suggest that RA showed its anticancer effect on cervical cancer cells by exhibiting cytotoxicity, inhibiting proliferation capacity, and inducing differentiation of cervical cancer cells. This finding shows that retinoic acid may potentially serve as a potent targeted therapy for cervical cancer and other cancers possessing CSCs within its tumors.  

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.

126 POTENTIAL EFFECTS OF ENGINEERED STEM CELLS TRANSDUCED WITH THERAPEUTIC GENES AGAINST HeLa HUMAN CERVICAL CANCER CELLS VIA A SELECTIVE TUMOR TROPISM CAUSED BY VASCULAR ENDOTHELIAL GROWTH FACTOR

2014 ◽  
Vol 26 (1) ◽  
pp. 177
Author(s):  
B.-R. Yi ◽  
S. U. Kim ◽  
K.-C. Choi
Keyword(s):  
Cervical Cancer ◽  
Stem Cells ◽  
Cell Viability ◽  
Cancer Cells ◽  
Real Time ◽  
Hela Cells ◽  
Real Time Pcr ◽  
Migration Assay ◽  
Cervical Cancer Cells ◽  
Human Cervical Cancer

According to the World Health Organization, cancer of cervix uteri is the second most common cancer among women worldwide. Recently, cervical cancer still remains a significant public health problem for women despite the development of the human papilloma virus vaccine. The aim of the present study was to investigate the therapeutic efficacy of genetically engineered stem cells (GESTEC) expressing bacterial cytosine deaminase (CD), human interferon-β (IFN-b) gene, or both against HeLa human cervical cancer and the migration factors of the GESTEC toward the cancer cells. A continuously dividing immortalized cell line of neural stem cells (NSC) from a single clone of human fetal brain, HB1.F3, was developed by introducing v-myc. The further introduction of these NSC with bacterial CD and human IFN-b resulted in the generation of HB1.F3.CD and HB1.F3.CD.IFN-b cells. The anticancer effect of these GESTEC was examined in a co-culture with HeLa cells using MTT assay to measure cell viability. A transwell migration assay was performed to assess the migration capability of the stem cells to cervical cancer cells. Next, several chemoattractant ligands and their receptors related to a selective migration of the stem cells towards HeLa cells were determined by real-time PCR. The cell viability of HeLa cells was decreased in response to 5-fluorocytosine (5-FC), a prodrug, indicating that 5-fluorouracil (5-FU), a toxic metabolite, was converted from 5-FC by the CD gene and it caused the cell death in a co-culture system. When IFN-b was additionally expressed with the CD gene by these GESTEC, the anticancer activity was significantly increased. In the migration assay, the GESTEC selectively migrated to HeLa cells. As results of real-time PCR, chemoattractant ligands such as MCP-1, SCF, and VEGF were expressed in HeLa cells, and several receptors such as uPAR, VEGFR2, and c-kit were produced by the GESTEC. These GESTEC transduced with the CD gene and IFN-b may provide the potential of a novel gene therapy for anti-cervical cancer treatments via their selective tumour tropism derived from VEGF and VEGFR2 expressions between HeLa cells and the GESTEC. This work was supported by a grant from the Next-Generation BioGreen 21 Program (No. PJ009599), Rural Development Administration, Republic of Korea.

scholarly journals [ARTICLE WITHDRAWN] Overexpression of MicroRNA-34a-5p Inhibits Proliferation and Promotes Apoptosis of Human Cervical Cancer Cells by Downregulation of Bcl-2

2018 ◽  
Vol 26 (6) ◽  
pp. 977-985 ◽  
Author(s):  
Xiufen Wang ◽  
Yucui Xie ◽  
Jing Wang
Keyword(s):  
Cervical Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Hela Cells ◽  
Cell Apoptosis ◽  
Migration And Invasion ◽  
Direct Target Gene ◽  
Cervical Cancer Cells ◽  
Mrna And Protein Expression ◽  
Human Cervical Cancer Cells

Aberrant expressions of microRNAs (miRNAs) are involved in the development and progression of various types of cancers. In this study, we investigated the roles of miR-34a-5p in the proliferation, migration, invasion, and apoptosis of cervical cancer cells (HeLa cells). We found that overexpression of miR-34a-5p significantly inhibited the viability, migration, and invasion of HeLa cells, but promoted cell apoptosis. Suppression of miR-34a-5p showed opposite effects. The mRNA and protein expression levels of Bcl-2 in HeLa cells were increased by miR-34a-5p suppression but decreased by miR-34a-5p overexpression. Bcl-2 was a direct target gene of miR-34a-5p, which participated in the effects of miR-34a-5p on HeLa cell viability, migration, invasion, and apoptosis. Suppression of miR-34a-5p promoted the viability, migration, and invasion of HeLa cells by increasing the expression of Bcl-2. Moreover, overexpression of Bcl-2 significantly promoted cell viability, migration, and invasion and had no influence on cell apoptosis. Suppression of Bcl-2 showed the opposite effects, with an increase in apoptosis. Overexpression of Bcl-2 activated the PI3K/AKT and JAK/STAT pathways in cervical cancer cells. Suppression of Bcl-2 inactivated the PI3K/AKT and JAK/STAT pathways in 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 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 Hexokinase 2 Promotes Cell Growth and Tumor Formation Through the Raf/MEK/ERK Signaling Pathway in Cervical Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Nan Cui ◽  
Lu Li ◽  
Qian Feng ◽  
Hong-mei Ma ◽  
Dan Lei ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Hela Cells ◽  
Tumor Formation ◽  
Erk Signaling ◽  
Cyclin A1 ◽  
Hexokinase 2 ◽  
Cervical Cancer Cells

Hexokinase 2 (HK2) is a member of the hexokinases (HK) that has been reported to be a key regulator during glucose metabolism linked to malignant growth in many types of cancers. In this study, stimulation of HK2 expression was observed in squamous cervical cancer (SCC) tissues, and HK2 expression promoted the proliferation of cervical cancer cells in vitro and tumor formation in vivo by accelerating cell cycle progression, upregulating cyclin A1, and downregulating p27 expression. Moreover, transcriptome sequencing analysis revealed that MAPK3 (ERK1) was upregulated in HK2-overexpressing HeLa cells. Further experiments found that the protein levels of p-Raf, p-MEK1/2, ERK1/2, and p-ERK1/2 were increased in HK2 over-expressing SiHa and HeLa cells. When ERK1/2 and p-ERK1/2 expression was blocked by an inhibitor (FR180204), reduced cyclin A1 expression was observed in HK2 over-expressing cells, with induced p27 expression and inhibited cell growth. Therefore, our data demonstrated that HK2 promoted the proliferation of cervical cancer cells by upregulating cyclin A1 and down-regulating p27 expression through the Raf/MEK/ERK signaling pathway.

scholarly journals Up-regulation of miRNA-148a inhibits proliferation, invasion, and migration while promoting apoptosis of cervical cancer cells by down-regulating RRS1

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Ying Zhang ◽  
Bingmei Sun ◽  
Lianbin Zhao ◽  
Zhengling Liu ◽  
Zonglan Xu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Hela Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Cervical Cancer Cells ◽  
And Migration

Abstract The purpose of the present study is to figure out the role of miRNA-148a (miR-148a) in growth, apoptosis, invasion, and migration of cervical cancer cells by binding to regulator of ribosome synthesis 1 (RRS1). Cervical cancer and adjacent normal tissues, as well as cervical cancer cell line Caski, HeLa, C-33A, and normal cervical epithelial cell line H8 were obtained to detect the expression of miR-148a and RRS1. Relationship between miR-148a and RRS1 expression with clinicopathological characteristics was assessed. The selected Caski and HeLa cells were then transfected with miR-148a mimics, miR-148a inhibitors or RRS1 siRNA to investigate the role of miR-148a and RRS1 on proliferation, apoptosis, colony formation, invasion, and migration abilities of cervical cancer cells. Bioinformatics information and dual luciferase reporter gene assay was for used to detect the targetting relationship between miR-148a and RRS1. Down-regulated miR-148a and up-regulated RRS1 were found in cervical cancer tissues and cells. Down-regulated miR-148a and up-regulated RRS1 are closely related with prognostic factors of cervical cancer. RRS1 was determined as a target gene of miR-148a and miR-148a inhibited RRS1 expression in cervical cancer cells. Up-regulation of miR-148a inhibited cell proliferation, migration, and invasion while promoting apoptosis in Caski and HeLa cells. Our study suggests that miR-148a down-regulates RRS1 expression, thereby inhibiting the proliferation, migration, and invasion while promoting cell apoptosis of cervical cancer cells.

Amiodarone’s major metabolite, desethylamiodarone, induces apoptosis in human cervical cancer cells

2018 ◽  
Vol 96 (10) ◽  
pp. 1004-1011 ◽  
Author(s):  
Zita Bognar ◽  
Katalin Fekete ◽  
Rita Bognar ◽  
Aliz Szabo ◽  
Reka A. Vass ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Hela Cell ◽  
Cancer Cells ◽  
Hela Cells ◽  
Dead Cell ◽  
Dependent Manner ◽  
Cervical Cancer Cells ◽  
Human Cervical Cancer Cells ◽  
Human Cervical Cancer

Previously, we found that desethylamiodarone (DEA) may have therapeutic potentiality in bladder cancer. In this study, we determined its effects on human cervical cancer cells (HeLa). Cell viability was evaluated by Muse Cell Count & Viability Assay; cell apoptosis was detected by Muse Annexin V & Dead Cell Assay. Cell cycle was flow cytometrically determined by Muse Cell Cycle Kit and the morphological changes of the cells were observed under a fluorescence microscope after Hoechst 33342 staining. The changes in the expression levels of apoptosis-related proteins in the HeLa cells were assessed by immunoblot. Our results showed that DEA significantly inhibited the proliferation and viability of HeLa cells and induced apoptosis in vitro in dose-dependent and also in cell cycle-dependent manner because DEA induced G0/G1 phase arrest in the HeLa cell line. We found that DEA treatment downregulated the expression of phospho-Akt and phospho-Bad. In addition, DEA could downregulate expression of Bcl-2, upregulate Bax, and induce cytochrome c release. Our results indicate that DEA might have significance as an anti-tumor agent against human cervical cancer.

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