scholarly journals Human Menstrual Blood-Derived Stem Cells Inhibit the Proliferation of HeLa Cells via TGF-β1-Mediated JNK/P21 Signaling Pathways

2019 ◽  
Vol 2019 ◽  
pp. 1-18
Author(s):  
Qian-Yu Liu ◽  
Feng Ruan ◽  
Jing-Yuan Li ◽  
Li Wei ◽  
Ping Hu ◽  
...  

Human menstrual blood-derived stem cells (hMBSCs) are a novel type of mesenchymal stem cells (MSCs) that have a high proliferative rate, multilineage differentiation potential, low immunogenicity, and low oncogenicity, making them suitable candidates for regenerative medicine. The therapeutic efficacy of hMBSCs has been demonstrated in some diseases; however, their effects on cervical cancer remain unclear. In the present study, we investigated whether hMBSCs have anticancer properties on cervical cancer cells in vivo and in vitro, which has not yet been reported. In vitro, transwell coculturing experiments revealed that hMBSCs suppress the proliferation and invasion of HeLa cervical cancer cells by inducing G0/G1 cell cycle arrest. In vivo, we established a xenografted BALB/c nude mouse model by subcutaneously coinjecting HeLa cells with hMBSCs for 21 days. We found that hMBSCs significantly decrease the average volume and average weight of xenografted tumors. ELISA, TGF-β1 antibody, and recombinant human TGF-β1 (rhTGF-β1) were used to analyze whether TGF-β1 contributed to cell cycle arrest. We found that hMBSC-secreted TGF-β1 and rhTGF-β1 induced cell cycle arrest and increased the expression of phospho-JNK and phospho-P21 in HeLa cells, which was mostly reversed by TGF-β1 antibody. These results indicate that hMBSCs have antitumor properties on cervical cancer in vitro and in vivo, mediated by the TGF-β1/JNK/p21 signaling pathway. In conclusion, this study suggests that hMBSC-based therapy is promising for the treatment of cervical cancer.

2020 ◽  
Vol 19 (7) ◽  
pp. 1423-1428
Author(s):  
Juan Li ◽  
Yuanyuan Chen

Purpose: To determine the anticancer effect of a pentacyclic triterpenoid, isomultiflorenol, against human cervical cancer.Methods: The proliferation of cancer cells was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) assay. Cell viability was measured with colony forming assay, while flow cytometry was used to study phase distribution in cancer cell mitosis. Electron microscopy was employed for the determination of autophagy induction in the cancer cells, while western blotting was used to assay protein expressions.Results: Isomultiflorenol significantly (p < 0.05) inhibited the proliferation and viability of cervical cancer cells in a concentration-dependent manner. The IC50 of isomultiflorenol was 10 μM for HeLa cells, and 90 μM for normal EV304 cells. The anti-proliferative effects were exerted as a result of arrest of HeLa cells at G2/M phase. The G2/M phase cells increased from 10.34 % in control to 30.21 % on treatment with 20 μM isomultiflorenol. Furthermore, administration of isomultiflorenol led to induction of cancer cell autophagy via mitochondrial apoptotic signaling.Conclusion: Isomultiflorenol inhibits human cervical cancer cells in vitro by inducing cell cycle arrest and autophagy. Thus, it is a potential lead molecule in the development of cervical cancer chemotherapy. Keywords: Cervical cancer, Terpenoids, Isomultiflorenol, Autophagy, Cell cycle arrest, Apoptosis


2016 ◽  
Vol 11 (4) ◽  
pp. 838 ◽  
Author(s):  
Ning Xia

<p class="Abstract">The present study was aimed at to demonstrate the antitumor effects of syringin in HeLa human cervical cancer cells. Its effects on apoptosis, cell cycle phase distribution as well as on cell migration were also examined. The effect on cell proliferation was evaluated by MTT assay, while as effects on colony formation were assessed using clonogenic assay. Syringin inhibited cancer cell growth in HeLa cells in a time-dependent as well as in a concentration-dependent manner. Syringin also led to inhibition of colony formation efficacy with complete suppression at 100 µM drug dose. Syringin could induce G2/M cell cycle arrest along with slight sub-G1 cell cycle arrest. HeLa cells began to emit red fluorescence as the dose of syringin increased from 0 µM in vehicle control to 100 µM. Syringin also inhibited cell migration in a dose-dependent manner with 100 µM dose of syringin leading to 100% inhibition of cell migration.</p><p> </p>


2018 ◽  
Vol 243 (14) ◽  
pp. 1133-1140
Author(s):  
Ling Chen ◽  
Ting Zhang ◽  
Qiuli Liu ◽  
Mei Tang ◽  
Yu’e Yang ◽  
...  

Buformin is a commonly used hypoglycemic agent, and numerous studies have shown that buformin has potent antitumor effects in several malignancies. In this study, we aimed to assess the cytotoxic effect of buformin combined with ionizing radiation (IR) on two human cervical cancer cell lines (Hela and Siha). Cytotoxicity was detected by colony formation assays; impacts on the cell cycle and apoptosis were detected by flow cytometric analyses. Changes in histone H2AX (γ-H2AX) phosphorylation and impacts on the AMPK/S6 pathway were also explored. Our data show that the combination of buformin and IR had a much stronger antiproliferative effect and resulted in more apoptosis than did buformin or IR alone. Combination treatment with a low dose of buformin (10 µM) and IR (4 Gy) caused G2/M-phase cell cycle arrest. Consistent with these findings, Western blotting showed that the combination of buformin and IR activated AMPK and suppressed S6. In addition, delayed disappearance of γ-H2AX was detected by immunofluorescence in cervical cancer cells treated with buformin plus IR. Taken together, the data indicate that the combination of a low concentration of buformin and IR increases the radiosensitivity of cervical cancer cells via cell cycle arrest and inhibition of DNA repair. Based on these results, we strongly support the use of buformin as an effective agent for improving IR treatment efficiency in the context of cervical cancer. Impact statement Our idea originated in the thought of discovering new effects of old drugs. Although this study is a basic research, it is very close to clinical treatment. Flow cytometry and immunofluorescence were used to verify that buformin increases radiosensitivity. We aimed to address one of the thorniest problems in treatment process. Based on discovering new effects of old drugs, it is feasible to use buformin as an anticancer drug in clinical application. This will provide new ideas for clinical treatment.


2018 ◽  
Vol 818 ◽  
pp. 124-131 ◽  
Author(s):  
Hongzhi Du ◽  
Yang Liu ◽  
Xudong Chen ◽  
Xiaowen Yu ◽  
Xiaoying Hou ◽  
...  

2020 ◽  
Author(s):  
Xiaofei Jiang ◽  
Mingqing Shi ◽  
Miao Sui ◽  
Yizhen Yuan ◽  
Shuang Zhang ◽  
...  

Abstract Background: Cervical cancer continues to be the leading cause of cancer deaths among women worldwide. Oleanolic acid (OA) is a naturally occurring substance found in the leaves, fruits, and rhizomes of plants that has anti-cancer activity. Methods: We used tumor-bearing mice as the animal model and Hela cell as cell models. Western blot was used for detecting the expression of proteins in ferroptosis related proteins acyl-CoA synthase long-chain family member 4 (ACSL4), ferritin heavy chain (FTH1), transferrin receptor (TfR1) and glutathione peroxidase 4 (GPX4) in vivo and in vitro. MTT and EdU was for the detection of the viability of Hela cells. Results: In vivo experiments showed that OA significantly reduced the size and mass of cervical cancer tumors. In vitro experiments showed that OA significantly reduced the viability and proliferation capacity of Hela cells. In both in vivo and in vitro assays, OA increased the level of oxidative stress and Fe2+ content, and increased the expression of ferroptosis related proteins. We found high expression of ACSL4 in both xenograft models and cervical carcinoma cells. Meanwhile, knockdown of ACSL4 expression using shRNA in cervical cancer cells significantly increased cell viability and proliferation. In addition, decreased ROS levels and GPX4 were detected in ACSL4 knockdown cervical cancer cells, suggesting that ACSL4 inhibition may contribute to the reduction of ferroptosis within Hela cells and thus improve Hela cell survival. Conclusion: Promotion of ACSL4 dependent ferroptosis through OA may be an effective approach to treat cervical cancer.


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