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 ◽  
...  

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.

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 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Ebtesam S. Al-Sheddi ◽  
Nida N. Farshori ◽  
Mai M. Al-Oqail ◽  
Shaza M. Al-Massarani ◽  
Quaiser Saquib ◽  
...  

In this study, silver nanoparticles (AgNPs) were synthesized using aqueous extract of Nepeta deflersiana plant. The prepared AgNPs (ND-AgNPs) were examined by ultraviolet-visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscope (SEM), and energy dispersive spectroscopy (EDX). The results obtained from various characterizations revealed that average size of synthesized AgNPs was 33 nm and in face-centered-cubic structure. The anticancer potential of ND-AgNPs was investigated against human cervical cancer cells (HeLa). The cytotoxic response was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), neutral red uptake (NRU) assays, and morphological changes. Further, the influence of cytotoxic concentrations of ND-AgNPs on oxidative stress markers, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), cell cycle arrest and apoptosis/necrosis was studied. The cytotoxic response observed was in a concentration-dependent manner. Furthermore, the results also showed a significant increase in ROS and lipid peroxidation (LPO), along with a decrease in MMP and glutathione (GSH) levels. The cell cycle analysis and apoptosis/necrosis assay data exhibited ND-AgNPs-induced SubG1 arrest and apoptotic/necrotic cell death. The biosynthesized AgNPs-induced cell death in HeLA cells suggested the anticancer potential of ND-AgNPs. Therefore, they may be used to treat the cervical cancer cells.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yi Hu ◽  
Yan Ma ◽  
Guifang Luo ◽  
Wenyan Liao ◽  
Shufen Zhang ◽  
...  

Yes-associated protein 1 (YAP1) is an important signaling pathway activator molecule. Studies have shown that it is involved in the occurrence of malignant tumors. This study identified a microRNA (miR/miRNA) targeting the 3′ untranslated region (3″ utr) of the YAP1 gene and evaluated its biological impact on human cervical cancer cells and related molecular mechanisms. qPCR and western blotting were used to detect the levels of miR-375 and YAP1 in HeLa cells. TargetScan software was used to identify the binding sites of YAP1 and miR-375. The MTT method was used to determine the viability of HeLa cells transfected with miR-375 mimic and YAP1 interference vector, the Transwell chamber experiment was used to detect the invasion of HeLa cells after transfection, the apoptosis of HeLa cells after transfection was detected by flow cytometry, and the western blotting was used to detect the epithelial mesenchymal transition (EMT) of HeLa cells after transfection. The expression of miR-375 in HeLa cells was significantly lower than that of normal control cervical cells, and the expression of YAP1 in HeLa cells was significantly higher than that of normal control cervical cells. TargetScan analysis showed that miR-375 was bound to the 3′ UTR of YAP1. qPCR and western blot analysis showed that transfection of miR-375 mimics inhibited YAP1 expression in HeLa cells. Transfection of miR-375 mimic and YAP1 interference vector inhibited HeLa cell invasion and EMT and promoted HeLa cell apoptosis. These findings indicate that miR-375 inhibits the malignant development of human cervical cancer cells by regulating the expression of YAP1.


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


Author(s):  
Xiaoling Wu ◽  
Zhiqin Yang ◽  
Huimin Dang ◽  
Huixia Peng ◽  
Zhijun Dai

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.


2020 ◽  
Vol 19 (1) ◽  
pp. 115-120
Author(s):  
Hai Yang ◽  
Jiyi Xia ◽  
Yan Li ◽  
Yong Cao ◽  
Li Tang ◽  
...  

Purpose: To identify the role of baicalein in human cervical cancer and to determine whether baicalein treatment affects hedgehog/Gli signaling pathway. Methods: Cell proliferation was evaluated by MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and colony formation assays. Cell death rate was assessed by PI-staining and FACS assay. Furthermore, cell invasion was assessed by Transwell assay while the levels of the key proteins were measured by western blotting analysis. Results: Baicalein suppressed the viability and proliferation of HeLa cells. The colony formation ability and relative migration rate were significantly decreased in the HeLa cells treated with 50 μM baicalein. Furthermore, the levels of Shh, Gli1, MMP-9, and VEGF declined significantly in baicalein-treated cells. Conclusion: The results demonstrate that baicalein inhibits the growth and invasiveness of cervical cancer cells partly by suppressing the activation of hedgehog/Gli signaling pathway in a concentrationdependent manner. Keywords: Cervical cancer, baicalein, hedgehog/Gli pathway, MMP-9


2014 ◽  
Vol 912-914 ◽  
pp. 1961-1964 ◽  
Author(s):  
Wei Zhang ◽  
Wen He Zhu ◽  
Yan Li ◽  
Jun Luo ◽  
Shi Jie Lv

Abstract: To investigate whether juglone could inhibits the proliferation on human cervical cancer cells (HeLa) in vitro. Cells were divided into control group, different concentration (10μM, 20μM, 50μM, 100μM and200μM) juglone groups for different durations. The viability of HeLa cells was detected by methyl thiazolyl tetrazolium (MTT) assay. The morphology changes of HeLa cells were observed by inverted microscope .The results showed that the viability of HeLa cells was decreased and the cell morphology was changed in a dose-dependent manner after treatment different concentration juglone for 24h when compared with control group. The results suggest that Juglone may be effective for the treatment of HeLa cells.


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