Mifepristone Inhibits the Migration of Cervical Cancer Cells by Inhibiting Exocrine Secretion

Pharmacology ◽  
2018 ◽  
Vol 101 (5-6) ◽  
pp. 322-329 ◽  
Author(s):  
Lin Sang ◽  
Xiaoyan Wang ◽  
Xingbo Zhao
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Hela Cells ◽  
Annexin V ◽  
Fluorescein Isothiocyanate ◽  
Exocrine Secretion ◽  
Migration Assay ◽  
Isg15 Expression ◽  
And Migration ◽  
Induced Apoptosis

Cervical cancer (CC) is one of the most common gynecological malignancies, and metastasis limits the use of surgical resection. Metapristone (MIF) was reported to suppress the proliferation and migration of several cancer cells. Exosomes play a variety of roles in cellular biological processes. The relation of exosomes and CC is less studied. Cell viability, apoptosis assay and migration assay was conducted in HeLa cells treated by MIF by CCK-8 kit, staining by Annexin V-fluorescein isothiocyanate and propidium iodide, and wound test respectively. ISG15 expression level was examined in MIF-treated HeLa cells by Western blot. The migration of HeLa cells treated by MIF/GW4869 was measured by wound test. MIF suppressed the growth and migration, as well as induced apoptosis of CC cells. MIF inhibited the exocrine secretion of CC cells by upregulating ISG15, while treating CC cells by ISG15 stimulus, IFN, inhibited the secretion of exosomes. The inhibition of exocrine secretion by GW4869 enhanced the migration inhibition of MIF on CC cells. This study demonstrates that MIF suppresses the CC cell migration by inhibiting exocrine secretion through upregulating ISG1.

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.

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.

scholarly journals Protein kinase C β inhibits autophagy and sensitizes cervical cancer Hela cells to cisplatin

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
Na Li ◽  
Wei Zhang
Keyword(s):  
Cervical Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Hela Cells ◽  
B Cell Lymphoma ◽  
Kinase C ◽  
Cervical Cancer Cells ◽  
Pkc Β ◽  
Induced Apoptosis

Recently, autophagy has been indicated to play an essential role in various biological events, such as the response of cervical cancer cells to chemotherapy. However, the exact signalling mechanism that regulates autophagy during chemotherapy remains unclear. In the present study, we investigated the regulation by cisplatin on protein kinase C β (PKC β), on B-cell lymphoma 2 (Bcl-2) and on apoptosis in cervical cancer Hela cells. And then we examined the regulation by cisplatin on autophagy and the role of autophagy on the chemotherapy in Hela cells. In addition, the regulation of the PKC β on the autophagy was also investigated. Our results indicated that cisplatin promoted PKC β in Hela cells. The PKC β inhibitor reduced the cisplatin-induced apoptosis, whereas increased the cisplatin-induced autophagy in Hela cells. On the other side, the PKC β overexpression aggravated the cisplatin-induced apoptosis, whereas down-regulated the cisplatin-induced autophagy. Taken together, our study firstly recognized the involvement of PKC β in the cytotoxicity of cisplatin via inhibiting autophagy in cervical cancer cells. We propose that PKC β would sensitize cervical cancer cells to chemotherapy via reducing the chemotherapy induced autophagy in cancer cells.

scholarly journals Assessment of Cytotoxic Activity of Rosemary (Rosmarinus officinalisL.), Turmeric (Curcuma longaL.), and Ginger (Zingiber officinaleR.) Essential Oils in Cervical Cancer Cells (HeLa)

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
P. A. S. R. Santos ◽  
G. B. Avanço ◽  
S. B. Nerilo ◽  
R. I. A. Marcelino ◽  
V. Janeiro ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Essential Oils ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Hela Cells ◽  
Membrane Integrity ◽  
Annexin V ◽  
Cervical Cancer Cells

The objective of this study was to evaluate the cytotoxic activity of rosemary (REO,Rosmarinus officinalisL.), turmeric (CEO,Curcuma longaL.), and ginger (GEO,Zingiber officinaleR.) essential oils in HeLa cells. Cytotoxicity tests were performedin vitro, using tetrazolium (MTT) and neutral red assays for evaluation of antiproliferative activity by different mechanisms, trypan blue assay to assess cell viability and evaluation of cell morphology for Giemsa to observe the cell damage, and Annexin V to evaluate cell death by apoptosis. CEO and GEO exhibited potent cytotoxic activity against HeLa cells. IC50obtained was 36.6 μg/mL for CEO and 129.9 μg/mL for GEO. The morphology of HeLa cells showed condensation of chromatin, loss of cell membrane integrity with protrusions (blebs), and cell content leakage for cells treated with CEO and GEO, from the lowest concentrations studied, 32.81 μg/mL of CEO and 32.12 μg/mL of GEO. The Annexin V assay revealed a profile of cell death by apoptosis for both CEO and GEO. The results indicate cytotoxic activityin vitrofor CEO and GEO, suggesting potential use as anticancer agents for cervical cancer cells.

scholarly journals A Litopenaeus vannamei Hemocyanin-Derived Antimicrobial Peptide (Peptide B11) Attenuates Cancer Cells’ Proliferation

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3202 ◽  
Author(s):  
Shangjie Liu ◽  
Jude Aweya ◽  
Liyuan Zheng ◽  
Fan Wang ◽  
Zhou Zheng ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Hela Cells ◽  
Litopenaeus Vannamei ◽  
Annexin V ◽  
B Cell Lymphoma ◽  
T Antigen ◽  
Cell Uptake ◽  
Normal Liver Cell ◽  
Induced Apoptosis

Antimicrobial peptides play important roles in the immune response to pathogens and tumor cells; for this reason, they are being exploited for therapeutic use. In this study, we describe a Litopenaeus vannamei hemocyanin-derived peptide, denoted B11, which shares similar features with other anticancer peptides and attenuates the proliferation of cancer cells. Cell viability assay revealed that B11 significantly inhibited the proliferation of human cervical (HeLa), human hepatocellular carcinoma (HepG2), and human esophageal cancer (EC109) cancer cell lines, but not normal liver cell lines (T-antigen-immortalized human liver epithelial (THLE) cells or THLE-3), by inducing morphological changes, nuclear condensation, and margination, features which are indicative of apoptosis. Besides, peptide B11-induced apoptosis was confirmed by isothiocyanate-labeled Annexin V/propidium iodide (Annexin V-FITC/PI) double staining of HeLa cells. Moreover, cell uptake studies, confocal microscopy, and Western blot analysis revealed that rhodamine-labeled B11 permeated HeLa cells and localized to the mitochondria, causing mitochondria dysfunction through lost mitochondrial membrane potential, which consequently triggered the induction of apoptosis. Increased expression levels of caspase-9, caspase-3, and Bax (Bcl-2-associated X) proteins, coupled with a decrease in Bcl-2 (B-cell lymphoma 2) protein, confirmed that peptide B11 induced apoptosis via the mitochondrial pathway. Thus, the hemocyanin-derived peptide, B11, inhibits the proliferation of cancer cells by causing mitochondrial dysfunction and inducing apoptotic cell death, for which reason it could be explored as an anticancer peptide.

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.

20(S)-ginsenoside Rh2-induced apoptosis and protective autophagy in cervical cancer cells by inhibiting AMPK/mTOR pathway

2021 ◽  
Author(s):  
Shuai Bian ◽  
Meichen Liu ◽  
Song Yang ◽  
Shuyan Lu ◽  
Siming Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Hela Cells ◽  
Biological Activities ◽  
Mtor Pathway ◽  
Ginsenoside Rh2 ◽  
Apoptotic Pathway ◽  
Cervical Cancer Cells ◽  
Induced Apoptosis ◽  
Apoptosis Inhibitor

Abstract 20(S)-Ginsenoside Rh2 (GRh2) has various biological activities including anticancer effects. However, no reports have investigated the connection between autophagy and apoptosis in HeLa cells treated with 20(S)-GRh2. In this study, We found that 20(S)-GRh2 suppressed proliferation and induced apoptosis in HeLa cells by activating the intrinsic apoptotic pathway and causing mitochondrial dysfunction. 20(S)-GRh2 enhanced cell autophagy through promoted the phosphorylation of AMPK, depressed the phosphorylation of AKT and suppressed mTOR activity. Furthermore, treatment with the autophagy inhibitor 3-MA enhanced 20(S)-GRh2-induced apoptosis, while the autophagy inducer rapamycin promoted cell survival. Moreover, the apoptosis inhibitor Z-VAD-FMK significantly restrained the apoptosis and autophagy induced by 20(S)-GRh2 in HeLa cells. We found that 20(S)-ginsenoside Rh2-induced protective autophagy promotes apoptosis of cervical cancer cells by inhibiting AMPK/mTOR pathway.

scholarly journals Circ SMARCA5 Inhibited Tumor Metastasis by Interacting with SND1 and Downregulating the YWHAB Gene in Cervical Cancer

2021 ◽  
Vol 30 ◽  
pp. 096368972098378
Author(s):  
Xia Zhang ◽  
Qing Zhang ◽  
Ke Zhang ◽  
Fang Wang ◽  
Xiaogai Qiao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Annexin V ◽  
Fluorescein Isothiocyanate ◽  
Cell Counting ◽  
Cervical Cancer Cells ◽  
Proliferation And Invasion

Cervical cancer is one of the diseases that seriously endanger women’s health. Circular RNA plays an important role in regulating the occurrence and development of cervical cancer. Here, we investigated the mechanisms of circ SMARCA5 in the development of cervical cancer. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) results showed that the expression of SMARCA5 was downregulated in cervical cancer tissues and cell lines. Then we found that overexpression of SMARCA5 inhibited proliferation and invasion, but promoted apoptosis in cervical cancer cells. These were detected by Cell Counting Kit-8, Transwell, and Annexin V-fluorescein isothiocyanate/propidium iodide detection kit, respectively, and the expression of the apoptosis-related proteins was determined by western blotting. Then we predicted that SMARCA5 combined with Staphylococcal nuclease domain-containing 1 (SND1) by starBase, and verified by RNA pull-down assay. To further reveal the molecular mechanisms of SMARCA5 in the progression of cervical cancer, the interaction protein of SND1 was predicted by STRING, and the interaction was verified by co-immunoprecipitation assay. Then, the effects of SND1 or YWHAB on the development of cervical cancer were detected by the gain and loss function test, and we found that knockdown of SND1 or YWHAB reversed the effects of SMARCA5 short interfering RNA on proliferation, invasion, and apoptosis of cervical cancer cells. Overexpression of SMARCA5 inhibited cervical cancer metastasis in vivo. Our results showed that overexpression of circ SMARCA5 inhibits the binding of SND1 to YWHAB, and inhibits the proliferation and invasion, but promotes apoptosis in cervical cancer cells, thus inhibiting the metastasis of cervical cancer.

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 Targeting the hallmarks of cancer: the effects of silibinin on proliferation, cell death, angiogenesis, and migration in colorectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Saba Sameri ◽  
Chiman Mohammadi ◽  
Mehrnaz Mehrabani ◽  
Rezvan Najafi
Keyword(s):  
Annexin V ◽  
Anticancer Activities ◽  
Scratch Assay ◽  
Anti Cancer ◽  
Different Types ◽  
Colon Cell ◽  
Colon Cell Line ◽  
And Migration ◽  
Induced Apoptosis ◽  
Colony Forming Assay

Abstract Background Silibinin, as a chemopreventive agent, has shown anti-cancer efficacy against different types of cancers. In the present study, we investigated the anti-cancer activities of silibinin on CT26 mouse colon cell line. Methods CT26 cells were treated with different concentrations of silibinin. To examine the cytotoxic effect of silibinin on proliferation, apoptosis, autophagy, angiogenesis, and migration, MTT, colony-forming assay, Annexin V/PI flow cytometry, RT-qPCR, and Scratch assay were used. Results Silibinin was found to significantly reduce CT26 cells survival. Furthermore, silibinin strongly induced apoptosis and autophagy by up-regulating the expression of Bax, Caspase-3, Atg5, Atg7 and BECN1 and down-regulating Bcl-2. Silibinin considerably down-regulated the expression of COX-2, HIF-1α, VEGF, Ang-2, and Ang-4 as well as the expression of MMP-2, MMP-9, CCR-2 and CXCR-4. Conclusions The present study revealed that silibinin shows anticancer activities by targeting proliferation, cell survival, angiogenesis, and migration of CT26 cells.

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