scholarly journals Baicalein Inhibits the Proliferation of Cervical Cancer Cells Through the GSK3β-Dependent Pathway

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.

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.


2019 ◽  
Vol 18 (2) ◽  
pp. 196-200
Author(s):  
Yu Lixiao ◽  
Liu Xiaoyun

Cervical cancer is one of the most malignant cancers of the female reproductive system with high morbidity and mortality. In the current study, we have examined the effect of eriodictyol on cell survival including cell growth, cell cycle and apoptosis of cervical cancer cells and also explored the underlying mechanism(s). To this end, CCK-8 assay, flow cytometry and western blotting assays were performed in cervical cancer HeLa cells. Eriodictyol significantly inhibited cell survival including impeding the cell viability, arresting the cell cycle at the G1 phase and potentiating cell apoptosis in a concentration-dependent manner. Also, ERI activated PTEN, P21, cleaved caspase-3/-9 expression and downregulated P-Akt and cyclin D1 expression in a dose-dependent manner. In conclusion, ERI can inhibit cervical cancer HeLa cells viability via impeding cell cycle and inducing apoptosis by regulating PTEN/Akt signaling pathway.


2016 ◽  
Vol 11 (2) ◽  
pp. 453 ◽  
Author(s):  
Yong Qian Xu ◽  
Jian Hai Zhang ◽  
Xing Sheng Yang

<p class="Abstract">The main objective of the present study was to investigate the anti-tumor activity of corosolic acid in CaSki human cervical cancer cells. Fluorescence and phase contrast microscopic techniques were used to study the effect of the compound on cellular morphology and apoptosis. Results revealed that corosolic acid exerted potent, dose- and time-dependent growth inhibitory effects in CaSki cell proliferation. Cells got detached from one another making clusters of small number of cells floating in the medium. After the cells were treated with 10, 50 and 100 µM concentrations of corosolic acid, cells began to emit orange red fluorescence more heavily at the centre of cells indicating apoptosis. Corosolic acid also induced G2/M cell cycle arrest in a dose-dependent manner. Increasing doses of corosolic acid treatment to these cells resulted in significant and dose-dependent down-regulation of PI3K and Akt protein expressions.</p><p><strong>Video Clip</strong></p><p><a href="https://youtube.com/v/N4EivZECRZE">Western blot assay</a>: 2 min 1 sec  </p>


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Wai Kuan Yong ◽  
Sri Nurestri Abd Malek

We investigate induction of apoptosis by xanthohumol on Ca Ski cervical cancer cell line. Xanthohumol is a prenylated chalcone naturally found in hop plants, previously reported to be an effective anticancer agent in various cancer cell lines. The present study showed that xanthohumol was effective to inhibit proliferation of Ca Ski cells based on IC50values using sulforhodamine B (SRB) assay. Furthermore, cellular and nuclear morphological changes were observed in the cells using phase contrast microscopy and Hoechst/PI fluorescent staining. In addition, 48-hour long treatment with xanthohumol triggered externalization of phosphatidylserine, changes in mitochondrial membrane potential, and DNA fragmentation in the cells. Additionally, xanthohumol mediated S phase arrest in cell cycle analysis and increased activities of caspase-3, caspase-8, and caspase-9. On the other hand, Western blot analysis showed that the expression levels of cleaved PARP, p53, and AIF increased, while Bcl-2 and XIAP decreased in a dose-dependent manner. Taken together, these findings indicate that xanthohumol-induced cell death might involve intrinsic and extrinsic apoptotic pathways, as well as downregulation of XIAP, upregulation of p53 proteins, and S phase cell cycle arrest in Ca Ski cervical cancer cells. This work suggests that xanthohumol is a potent chemotherapeutic candidate for 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>


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Atchara Chothiphirat ◽  
Kesara Nittayaboon ◽  
Kanyanatt Kanokwiroon ◽  
Theera Srisawat ◽  
Raphatphorn Navakanitworakul

Vatica diospyroides Symington is locally known as Chan-Ka-Pho in Thailand. Ancient people have used it as therapeutic plant for cardiac and blood tonic cure. The purpose of this study was to investigate the potential cytotoxicity and selectivity of the extracts from V. diospyroides type SS fruit on cervical cancer HeLa and SiHa cell lines and to examine its underlying mechanism of action. MTT assay revealed that the extracts showed inhibition of cell survival in a dose-dependent manner and exhibited highly cytotoxic activity against both HeLa and SiHa cells with IC50 value less than 20 μg/mL along with less toxicity against L929 cells. Acetone cotyledon extract (ACE) showed the best selectivity index value of 4.47 (HeLa) and 3.51 (SiHa). Distinctive morphological changes were observed in ACE-treated cervical cancer cells contributing to apoptosis action. Flow cytometry analysis with Annexin V-FITC and PI staining precisely indicated that ACE induced apoptosis in HeLa and SiHa cell lines in a dose-dependent manner. Treatment of ACE with half IC50 caused DNA fragmentation and also activated increasing of bax and cleaved caspase-8 protein in HeLa cells after 48 h exposure. The results suggest that ACE has potent and selective cytotoxic effect against cervical cancer cells and the potential to induce bax and caspase-8-dependent apoptosis. Hence, the ACE could be further exploited as a potential lead in cancer treatment.


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.


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.


2020 ◽  
Author(s):  
Ting Cai ◽  
Wenquan Wu ◽  
Qiang Ming ◽  
Longhua Guo ◽  
Yongwu Xia ◽  
...  

Abstract Notoginsenoside R1 (NGR1) is isolated from the panax notoginseng which is a kind of Traditional Chinese Medicine and edible plant with good healthful effect that using range is very wide for medical treatment and health care. It had been demonstrated to inhibit various tumors proliferation, but whether it inhibited cervical cancer cells proliferation and its mechanism was not unclear. In this study, we showed that NGR1 could inhibit cervical cancer cells to proliferate with a time and dose dependent manner, induce cervical cancer cells apoptosis and arrest cervical cancer cells in G1/S-phase . We also found that NGR1 could make H2AX phosphorylation and inhibit PHF6 expression with a time and dose dependent manner. Furthermore, when over expression PHF6 gene, the γH2AX haven't any change , but silenced PHF6 gene with siRNA, the γH2AX increased significantly. That mean PHF6 has negative correlation with γH2AX. Subsequently , we added NGR1 to intervene, something interesting happened that PHF6 protein fell even more, but the γH2AX more up regulation in the siPHF6 and NGR1 group. In the PEGFP-C1-PHF6 plasmid vector and NGR1 group, inversely , the PHF6 protein declined, and the γH2AX still up regulation . All those results indicate d that NGR1 caused DNA injury by inhibiting PHF6 activity pathway and arrested cervical cancer cells in G1/S-phase.


2021 ◽  
Vol 18 (7) ◽  
pp. 1455-1460
Author(s):  
Songnian Liang ◽  
Linlin Liu

Purpose: To investigate the anticancer effects of sparteine against human cervical cancer. Methods: Cell viability was determined by CCK8 assay, while 4′, 6-diamidino-2-phenylindole (DAPI) staining was used for determination of apoptosis. Cell cycle analysis was done with flow cytometry, while cell invasion was monitored using Transwell invasion assays. Protein expressions were determined using Western blotting. Results: The results revealed that sparteine inhibited the viability of cervical cancer cells with halfmaximal inhibitory concentration (IC50) ranging from 10 to 25 µM. Sparteine exerted more profound antiproliferative effects on DoTc2 cells, with IC50 of 10 µM. However, minimal cytotoxicity was observed in normal cervical cells, as evident from the IC50 of 80 µM. Sparteine triggered the generation of ROS and apoptotic cell death in DoTc2 cells. The induction of apoptosis was accompanied by upregulation of Bax expression and downregulation of Bcl-2 expression. Sparteine caused arrest of DoTc2 cells at the G0/G1 phase of the cell cycle, and suppressed the expressions of cyclin A and cyclin B1. Transwell assay data showed that sparteine decreased the invasion ability of DoTc2 cells. Sparteine also inhibited the phosphorylation of VGFR2 in a concentration-dependent manner. Conclusion: Sparteine exhibits significant anticancer activity and may prove beneficial in cervical cancer chemotherapy.


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