Effects of Ginkgolide B on the Proliferation and Apoptosis of Cervical Cancer Cells

Cervical cancer is the fourth most common cancer among women worldwide. The treatment of cervical cancer mainly focused on surgery and radiotherapy, whereas the prognosis of invasive cervical cancer is still low. Ginkgo biloba is an ancient medicinal plant that has been used for decades to treat ischemic strokes and cognitive decline. Ginkgolide B, an active ingredient extracted from Ginkgo biloba, has multiple biological activities such as antioxidant, anti-apoptotic, and anti-inflammatory effects. Ginkgolide B has been found to have anti-tumor effects and inhibits the progression of multiple types of cancers. However, its potential role in cervical cancer is still unclear. In this study, we found that ginkgolide B suppresses the proliferation of cervical cancer cells in a dose-dependent manner. Ginkgolide B also induces cell cycle arrest and stimulates cell apoptosis by modulating the MAPK signaling pathway. We, therefore, present a novel and promising anti-tumor drug for the treatment of cervical cancer.

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Shikonin Inhibits The Proliferation of Cervical Cancer Cells Via FAK/AKT/GSK3β Signalling

10.21203/rs.3.rs-1151972/v1 ◽

2021 ◽

Author(s):

Ziyan Xu ◽

Liru Huang ◽

Tiantian Zhang ◽

Yuwei Liu ◽

Mei Gong ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Biological Activities ◽

Inhibitory Effect ◽

Dependent Manner ◽

Inhibitory Effects ◽

Cervical Cancer Cells ◽

And Migration

Abstract Cervical cancer is one of the most common female cancers worldwide, and it is one of the most lethal malignancies of the female reproductive system. Shikonin, a natural pigment of theophyllin, has a variety of biological activities and has shown significant inhibitory effects on a variety of tumours in vitro and in vivo. However, there are few studies on Shikonin in cervical cancer. In the present study, we found that Shikonin inhibited not only the proliferation but also the migration of cervical cancer cells. Our data showed that Shikonin inhibited the proliferation of HeLa and SiHa cells in a concentration- and time-dependent manner. In cervical cancer cells, Shikonin not only inhibited the phosphorylation of FAK, AKT and GSK3β but also inhibited the phosphorylation of FAK, AKT and GSK3β induced by EGF. Further exploring the mechanism, we found that Shikonin could inhibit the proliferation of cervical cancer cells by regulating the phosphorylation of the FAK/AKT/GSK3β pathway. In addition, Shikonin significantly inhibited cell migration and reduced the expression of proteins such as MTA1, TGFβ1 and VEGF. In conclusion, our study elucidated that Shikonin has an inhibitory effect on the proliferation and migration of cervical cancer cells, which may be mediated by the FAK/AKT/GSK3β signalling pathway. Our results suggest that Shikonin has the potential to become a clinical treatment for cervical cancer.

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Corosolic acid induces potent anti-cancer effects in CaSki cervical cancer cells through the induction of apoptosis, cell cycle arrest and PI3K/Akt signalling pathway

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v11i2.26793 ◽

2016 ◽

Vol 11 (2) ◽

pp. 453 ◽

Cited By ~ 2

Author(s):

Yong Qian Xu ◽

Jian Hai Zhang ◽

Xing Sheng Yang

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Video Clip ◽

Dependent Manner ◽

Cycle Arrest ◽

Corosolic Acid ◽

Cervical Cancer Cells ◽

Dose Dependent

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.Video Clip<a href="https://youtube.com/v/N4EivZECRZE">Western blot assay</a>: 2 min 1 sec

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Anti-Cancerous Effect of Rutin Against HPV-C33A Cervical Cancer Cells via G0/G1 Cell Cycle Arrest and Apoptotic Induction

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190806122257 ◽

2020 ◽

Vol 20 (3) ◽

pp. 409-418 ◽

Cited By ~ 8

Author(s):

Fahad Khan ◽

Pratibha Pandey ◽

Tarun K. Upadhyay ◽

Asif Jafri ◽

Niraj K. Jha ◽

...

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cell Cycle Arrest ◽

Biological Activities ◽

Dependent Manner ◽

Nuclear Condensation ◽

Therapeutic Role ◽

Cycle Arrest ◽

Cervical Cancer Cells

Background: Nowadays, the potential therapeutic role of various bioflavonoids including Curcumin, Luteolin and Resveratrol has currently been well-documented in a vast range of fatal complications including synaptic failure and cancers. These bioflavonoids are widely being implemented for the treatment of various cancers as they possess anti-cancerous, anti-oxidant and anti-inflammatory properties. Moreover, they are also used as a better alternative to conventional therapies since; these are non-toxic to cells and having no or least side effects. Notably, the pertinent therapeutic role of Rutin in cervical cancer is still unsettled however, its anti-cancerous role has already been reported in other cancers including prostate and colon cancer. Rutin (Vitamin P or Rutoside) is a polyphenolics flavonoid exhibiting multi-beneficial roles against several carcinomas. Objective: Despite the evidence for its several biological activities, the anticancer effects of Rutin on human cervical cancer (C33A) cells remain to be explored. In this study, the anticancer potential of Rutin was investigated by employing the key biomarkers such as nuclear condensation reactive oxygen species (ROS), apoptosis, and changes in mitochondrial membrane potential (MMP). Results: Our findings showed that Rutin treatment reduced the cell viability, induced significant increase in ROS production and nuclear condensation in dose-dependent manner. Moreover, Rutin provoked apoptosis by inducing decrease in MMP and activation of caspase-3. Cell cycle analysis further confirmed the efficacy of Rutin by showing cell cycle arrest at G0/G1 phase. Conclusion: Thus, our study is envisaged to open up interests for elucidating Rutin as an anticancerous agent against cervical cancer.

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Xanthohumol Induces Growth Inhibition and Apoptosis in Ca Ski Human Cervical Cancer Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/921306 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 13

Author(s):

Wai Kuan Yong ◽

Sri Nurestri Abd Malek

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Morphological Changes ◽

S Phase ◽

Phase Cell ◽

Cervical Cancer Cell Line ◽

Dependent Manner ◽

Cervical Cancer Cells

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.

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Quantification of DNA double-strand break induced by radiation in cervix cancer cells: in vitro study

Journal of Radiotherapy in Practice ◽

10.1017/s1460396918000456 ◽

2018 ◽

Vol 18 (1) ◽

pp. 52-54

Author(s):

Sothing Vashum ◽

Rabi Raja Singh I ◽

Saikat Das ◽

Mohammed Azharuddin KO ◽

Prabhakaran Vasudevan

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Strand Break ◽

Double Strand Break ◽

Ionising Radiation ◽

Dependent Manner ◽

Survival Fraction ◽

Dna Double Strand Break ◽

Cervical Cancer Cells

AbstractAimDNA double-strand break (DSB) results in the phosphorylation of the protein, H.2AX histone. In this study, the effect of radiotherapy and chemotherapy on DNA DSB in cervical cancer cells is analysed by the phosphorylation of the protein.MethodsThe cervical cancer cells (HeLa cells) were cultured and exposed to ionising radiation. Radiation sensitivity was measured by clonogenic survival fraction after exposing to ionising radiation. Since the phosphorylation of H.2AX declines with time, the DNA damage was quantified at different time points: 1 hour, 3 hours and 1 week after exposed to the radiation. The analysis of γ-H.2AX was done by Western-blot technique. The protein expression was observed at different dose of radiation and combination of both radiation and paclitaxel.ResultsLow-dose hypersensitivity was observed. By 1 week after radiation at 0·5, 0·8 and 2 Gy, there was no expression of phosphorylated H.2AX. Previous experiments on the expression of phosphorylated H.2AX (γ-H.2AX) in terms of foci analysis was found to peak at 1 hour and subsequently decline with time. In cells treated with the DNA damaging agents, the expression of phosphorylated H.2AX decreases in a dose-dependent manner when treated with radiation alone. However, when combined with paclitaxel, at 0·5 Gy, the expression peaked and reduces at 0·8 Gy and slightly elevated at 2 Gy.FindingsIn this study, the peak phosphorylation was observed at 3 hour post irradiation indicating that DSBs are still left unrepaired.

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

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504017x15031557924141 ◽

2018 ◽

Vol 26 (4) ◽

pp. 645-653 ◽

Cited By ~ 4

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.

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Syringin exhibits anticancer effects in HeLa human cervical cancer cells by inducing apoptosis, cell cycle arrest and inhibition of cell migration

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v11i4.27755 ◽

2016 ◽

Vol 11 (4) ◽

pp. 838 ◽

Cited By ~ 3

Author(s):

Ning Xia

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cell Migration ◽

Cell Cycle Arrest ◽

Hela Cells ◽

Dependent Manner ◽

Cycle Arrest ◽

Cervical Cancer Cells ◽

Human Cervical Cancer Cells ◽

Human Cervical Cancer

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.

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Hesperidin Induces Mitochondria Mediated Intrinsic Apoptosis in HPV-positive Cervical Cancer Cells via Regulation of E6/p53 Expression

10.21203/rs.3.rs-105340/v1 ◽

2020 ◽

Author(s):

Fang Ren ◽

Gong Zhang ◽

Caiyu Li ◽

Gailing Li ◽

Yuan Cao ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Protein Level ◽

Potential Candidate ◽

Dependent Manner ◽

Antitumor Effects ◽

P53 Expression ◽

Cervical Cancer Cells ◽

Apoptotic Proteins

Abstract Background: Hesperetin, an active compound found in citrus fruits, possesses antiproliferative effects toward several types of cancer cell lines, including cervical cancer. In this study, we explore the antitumor effects of Hesperetin on the human cervical cancer human papilloma virus (HPV)-positive (CaSki and HeLa) and HPV-negative (C-33A) cell lines and further elucidated the underlying mechanisms of this action. Methods: Cell viability and proliferation was measured by the MTT assay and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay, respectively. dUTP-fluorescein nick end-labeling (TUNEL) staining, Annexin V‑fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining and flow cytometry was used to assess the degree of apoptosis. JC-1 staining assay was used to evaluate the change of mitochondrial membrane potential (ΔΨm) and Western blot assays were used to determine apoptosis-related factors at protein level. Results: Hesperetin (100, 200 and 400 μM) exhibited a significant exclusive inhibitory effect against the growth of HPV-infected CaSki and HeLa cancer cells via induction of apoptosis in a concentration-dependent manner, while it was almost not active in HPV-negative C-33A cancer cells and normal cervix epithelial H8 cells. Moreover, this antitumor effect executed by Hesperetin was associated with disruption of ΔΨm, the release of cytochrome c from mitochondria, activation of pro-apoptotic proteins (Bax, cleaved caspase-3 and caspase-9) and inhibition of anti-apoptotic proteins (Bcl-2). During this process, cleaved caspase-8 remained unchanged. In addition, Hesperetin led to a downregulation of E6 oncoprotein expression and upregulation of tumor suppressor protein p53 level. Conclusions: Collectively, these results implicated that Hesperetin can induce apoptosis of HPV‑positive cervical cancer cells via a mitochondria-mediated intrinsic signaling pathway, together with the repression of E6 and enhancement of p53 protein level, indicating Hesperetin may be considered as a potential candidate for the development of innovative anti-HPV cervical cancer agents.

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Buformin increases radiosensitivity in cervical cancer cells via cell-cycle arrest and delayed DNA-damage repair

Experimental Biology and Medicine ◽

10.1177/1535370218813320 ◽

2018 ◽

Vol 243 (14) ◽

pp. 1133-1140

Author(s):

Ling Chen ◽

Ting Zhang ◽

Qiuli Liu ◽

Mei Tang ◽

Yu’e Yang ◽

...

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Clinical Treatment ◽

Phase Cell ◽

Antitumor Effects ◽

Cycle Arrest ◽

Cervical Cancer Cells ◽

Old Drugs

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.

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