Oleanen Induces Apoptosis of Cervical Cancer Cells by Up-Regulation of Bim

ObjectivePlants belonging to the genus Celastrus exhibit antitumor activity and the ability to reverse multidrug resistance in tumor cells; however, it remains unclear whether the compound oleanen from Celastrus hypoleucus also exhibits antitumor activity. The objective of this study was to explore the inhibitory effect of 12-oleanene-3β, 6α-diol (oleanen) on the proliferation of cervical cancer HeLa cells in vitro, as well as its relative mechanism.MethodsHeLa cells were treated with different concentrations of oleanen for different times. Cell proliferation was determined by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide assay. Cell apoptosis was evaluated by flow cytometry and caspases activities assay. The expression of several proapoptotic proteins belonging to the Bcl-2 family, such as Bax, Bim, and Bad, was detected by Western blot.ResultsOleanen mainly inhibited the proliferation of HeLa cells at the G0 to G1 and G2 to M phases, and the IC50 of oleanen for cells was significantly higher at 24 hours compared to 48 hours (17.45 ± 3.71 vs 9.02 ± 0.83 μg/mL, respectively; P < 0.05). The significant increase in activity of caspase 3/7, caspase 6 in oleanen-treated HeLa cells indicated that oleanen promoted the apoptosis of HeLa cells. The activity of caspase 9 representing the endogenous apoptotic pathways also increased obviously in oleanen treatment. Furthermore, the increase in the expression of Bim was the most significant among the Bcl-2 family after oleanen treatment.ConclusionOleanen up-regulates the expression of Bim and other proapoptotic molecules to activate the endogenous apoptosis pathway, thus promoting apoptosis and inhibiting proliferation of human cervical cancer HeLa cells in vitro.

Download Full-text

Apoptotic effect of novel pyrazolone-based derivative [Cu(PMPP-SAL)(EtOH)] on HeLa cells and its mechanism

Scientific Reports ◽

10.1038/s41598-020-75173-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Delizhaer Reheman ◽

Jing Zhao ◽

Shan Guan ◽

Guan-Cheng Xu ◽

Yi-Jie Li ◽

...

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Hela Cells ◽

Copper Complexes ◽

Antibacterial Properties ◽

Inhibitory Effect ◽

Parp Cleavage ◽

Potential Candidate ◽

Tnf Α

Abstract Pyrazolone complexes have strong anti-tumor and antibacterial properties, but the anti-tumor mechanism of pyrazolone-based copper complexes has not been fully understood. In this study, the possible mechanism and the inhibitory effect of a novel pyrazolone-based derivative compound [Cu(PMPP-SAL)(EtOH)] on human cervical cancer cells (HeLa cells) was investigated. [Cu(PMPP-SAL)(EtOH)] effectively inhibited proliferation of HeLa cells in vitro with an IC50 value of 2.082 after treatment for 72 h. Cell cycle analysis showed apoptosis was induced by blocking the cell cycle in the S phase. [Cu(PMPP-SAL)(EtOH)] promoted the loss of mitochondrial membrane potential, release of cytochrome c, PARP cleavage, and activation of caspase-3/9 in HeLa cells. Additionally, [Cu(PMPP-SAL)(EtOH)] inhibited the PI3K/AKT pathway and activated the P38/MAPK, and JNK/MAPK pathways. [Cu(PMPP-SAL)(EtOH)] also inhibited the phosphorylation of Iκ-Bα in the NF-κB pathway activated by TNF-α, thus restricting the proliferation of HeLa cells which were activated by TNF-α. In conclusion, [Cu(PMPP-SAL)(EtOH)] inhibited the growth of HeLa cells and induced apoptosis possibly via the caspase-dependent mitochondria-mediated pathway. These results suggest that [Cu(PMPP-SAL)(EtOH)] can be a potential candidate for the treatment of cervical cancer.

Download Full-text

Effect of Superparamagnetic DMSO@γ-Fe2O3 Combined with Carmustine on Cervical Cancer

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2021.18596 ◽

2021 ◽

Vol 21 (12) ◽

pp. 6196-6204

Author(s):

Shu Wen ◽

Weiping Xing ◽

Lingxue Gao ◽

Shuping Zhao

Keyword(s):

Cervical Cancer ◽

Toxic Effect ◽

Cancer Cells ◽

Colorimetric Method ◽

Inhibitory Effect ◽

Magnetic Nanomaterials ◽

Combined Chemotherapy ◽

Killing Effect ◽

Cervical Cancer Cells

This study aimed to investigate the effects of DMSO@γ-Fe2O3 nanomagnetic fluid thermotherapy combined with the chemotherapy drug carmustine on cervical cancer cells under a certain intensity of alternating magnetic field. And the role of Mir-590-3P in the development and progression of cervical cancer. The optimal thermotherapy concentration of γ-Fe2O3 nanomaterials on cervical cancer cells was determined by in vitro heating. In addition, the MTT colorimetric method was used to evaluate the toxic effect of γ-Fe2O3 magnetic nanoparticles on cervical cancer cells, and the optimal therapeutic concentration of carbachol on cervical cancer cells was optimized (0.015 g · L−1). The cervical cancer cells were divided into control, γ-Fe2O3 hyperthermia, chemotherapy, and DMSO@γ-Fe2O3 combined chemotherapy groups. After 2 h exposure to hypothermic conditions, flow cytometry was used to assess cell apoptosis for each group. The heating effect of the γ-Fe2O3 magnetic nanomaterials was apparent. When the concentration of γ-Fe2O3 was ≥6 g· L−1, the temperature rise above 41 °C. γ-Fe2O3 is non-toxic to cervical cancer cells and has good biocompatibility. Taking the drug concentration of IC25 as the working concentration of this study, the working concentration of carmustine was 0.015 g · L−1. Both the 41 °C heat treatment and chemotherapy alone had a killing effect on glioma and cervical cancer cells (P < 0.05). Additionally, the combined inhibitory effect of DMSO@γ-Fe2O3 nanomagnetic fluid thermotherapy and drugs at this temperature was significantly stronger than that of thermotherapy and chemotherapy alone (P < 0.05). For the control, gamma-Fe2O3 hyperthermia, chemotherapy, and DMSO@γ-Fe2O3 combined chemotherapy groups, the apoptosis rates of the cervical cancer cells were 1.4%, 18.6%, 24.12%, and 38.97%, respectively. DMSO@γ-Fe2O3 nanomagnetic fluid thermotherapy combined with the chemotherapeutic drug carmustine exerted a noticeable toxic effect on the cervical cancer cells, and DMSO@γ-Fe2O3 significantly enhanced the killing effect of carmustine on cervical cancer cells.

Download Full-text

Oncolytic Vaccinia Virus Harboring Aphrocallistes vastus Lectin Inhibits the Growth of Cervical Cancer Cells Hela S3

Marine Drugs ◽

10.3390/md19100532 ◽

2021 ◽

Vol 19 (10) ◽

pp. 532

Author(s):

Jiajun Ni ◽

Hualin Feng ◽

Xiang Xu ◽

Tingting Liu ◽

Ting Ye ◽

...

Keyword(s):

Cervical Cancer ◽

Vaccinia Virus ◽

Cancer Cells ◽

Inhibitory Effect ◽

Genes Encoding ◽

Cervical Cancer Cells ◽

Hela S3 ◽

Hela S3 Cells

Aphrocallistes vastus lectin (AVL) is a C-type marine lectin produced by sponges. Our previous study demonstrated that genes encoding AVL enhanced the cytotoxic effect of oncolytic vaccinia virus (oncoVV) in a variety of cancer cells. In this study, the inhibitory effect of oncoVV-AVL on Hela S3 cervical cancer cells, a cell line with spheroidizing ability, was explored. The results showed that oncoVV-AVL could inhibit Hela S3 cells growth both in vivo and in vitro. Further investigation revealed that AVL increased the virus replication, promote the expression of OASL protein and stimulated the activation of Raf in Hela S3 cells. This study may provide insight into a novel way for the utilization of lection AVL.

Download Full-text

Swertiamarin exerts anticancer effects on human cervical cancer cells via induction of apoptosis, inhibition of cell migration and targeting of MEK-ERK pathway

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v20i1.12 ◽

2021 ◽

Vol 20 (1) ◽

pp. 75-81

Author(s):

Xinxiang Wang ◽

Tao Wang

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Western Blotting ◽

Hela Cells ◽

Migration And Invasion ◽

Inhibition Of Proliferation ◽

Anticancer Effects ◽

Cervical Cancer Cells ◽

Human Cervical Cancer

Purpose: To investigate the anticancer effects of swertiamarin against taxol- resistant human cervical cancer cells.Method: Cell viability was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5–diphenyl tetrazolium bromide (MTT) assay while colony survival was evaluated by clonogenic assay. Apoptotic cell death was assessed by AO/ETBR staining and western blotting techniques. The levels of reactive oxygen species (ROS) were measured using 2,7, dicholoro dihydrofluoresceindiacetate (H2DCFDA) staining.Cell migration and invasion were monitored with Transwell chamber assay. Western blotting assay was used to determine the expression levels of proteins of the MEK/ERK signaling pathway.Results: Swertiamarin induced dose- and time-dependent inhibition of proliferation of HeLa cervical cancer cells (p < 0.05). It also suppressed the colony formation potential of HeLa cells, and induced various structural modifications in HeLa cells. Swertiamarin exposure resulted in the formation of earlyapoptotic, late-apoptotic and necrotic cells, and significant modulation of apoptosis-allied proteins. It was observed that the migration and invasion of HeLa cells were potentially suppressed in dose-reliant fashion by swertiamarin. Western blotting results showed that the expressions of p-MEK and p-ERK were markedly reduced, while those of MEK and ERK were unaffected (p < 0.05).Conclusion: Swertiamarin exerts in vitro anticancer activity against cervical cancer cells (HeLa). Thus, it is promising for use in cervical cancer chemotherapy. However, there is need for confirmation of these findings through further in vivo and in vitro investigations. Keywords: Swertiamarin, Gentianaceae, Triterpene Sapogenin, Cervical cance

Download Full-text

Oleanolic acid inhibits the proliferation of Hela cells in cervical cancer by regulating the ACSL4 ferroptosis signaling pathway

10.21203/rs.3.rs-102345/v1 ◽

2020 ◽

Author(s):

Xiaofei Jiang ◽

Mingqing Shi ◽

Miao Sui ◽

Yizhen Yuan ◽

Shuang Zhang ◽

...

Keyword(s):

Cervical Cancer ◽

Hela Cell ◽

Cancer Cells ◽

Oleanolic Acid ◽

Hela Cells ◽

Proliferation Capacity ◽

Cervical Cancer Cells ◽

Related Proteins

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.

Download Full-text

Redox-Sensitive and Folate-Receptor-Mediated Targeting of Cervical Cancer Cells for Photodynamic Therapy Using Nanophotosensitizers Composed of Chlorin e6-Conjugated β-Cyclodextrin via Diselenide Linkage

Cells ◽

10.3390/cells10092190 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2190

Author(s):

Howard Kim ◽

Mi Woon Kim ◽

Young-IL Jeong ◽

Hoe Saeng Yang

Keyword(s):

Cervical Cancer ◽

Photodynamic Therapy ◽

Hela Cells ◽

Folate Receptor ◽

Chlorin E6 ◽

Ros Generation ◽

Cervical Cancer Cells ◽

Poly Ethylene

The aim of this study was to fabricate a reactive oxygen species (ROS)-sensitive and folate-receptor-targeted nanophotosensitizer for the efficient photodynamic therapy (PDT) of cervical carcinoma cells. Chlorin e6 (Ce6) as a model photosensitizer was conjugated with succinyl β-cyclodextrin via selenocystamine linkages. Folic acid (FA)-poly(ethylene glycol) (PEG) (FA-PEG) conjugates were attached to these conjugates and then FA-PEG-succinyl β-cyclodextrin-selenocystamine-Ce6 (FAPEGbCDseseCe6) conjugates were synthesized. Nanophotosensitizers of FaPEGbCDseseCe6 conjugates were fabricated using dialysis membrane. Nanophotosensitizers showed spherical shapes with small particle sizes. They were disintegrated in the presence of hydrogen peroxide (H2O2) and particle size distribution changed from monomodal distribution pattern to multimodal pattern. The fluorescence intensity and Ce6 release rate also increased due to the increase in H2O2 concentration, indicating that the nanophotosensitizers displayed ROS sensitivity. The Ce6 uptake ratio, ROS generation and cell cytotoxicity of the nanophotosensitizers were significantly higher than those of the Ce6 itself against HeLa cells in vitro. Furthermore, the nanophotosensitizers showed folate-receptor-specific delivery capacity and phototoxicity. The intracellular delivery of nanophotosensitizers was inhibited by folate receptor blocking, indicating that they have folate-receptor specificity in vitro and in vivo. Nanophotosensitizers showed higher efficiency in inhibition of tumor growth of HeLa cells in vivo compared to Ce6 alone. These results show that nanophotosensitizers of FaPEGbCDseseCe6 conjugates are promising candidates as PDT of cervical cancer.

Download Full-text

Proliferation Inhibition and Apoptosis Induction of Juglone on Human Cervical Cancer HeLa Cells

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.912-914.1961 ◽

2014 ◽

Vol 912-914 ◽

pp. 1961-1964 ◽

Cited By ~ 1

Author(s):

Wei Zhang ◽

Wen He Zhu ◽

Yan Li ◽

Jun Luo ◽

Shi Jie Lv

Keyword(s):

Cervical Cancer ◽

Hela Cells ◽

Control Group ◽

Dependent Manner ◽

Inverted Microscope ◽

Cervical Cancer Cells ◽

Human Cervical Cancer Cells ◽

Dose Dependent ◽

Human Cervical Cancer

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.

Download Full-text

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

The Scientific World JOURNAL ◽

10.1155/2016/9273078 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 7

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.

Download Full-text

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.

Download Full-text

A Novel Imidazopyridine Derivative Exerts Anticancer Activity by Inducing Mitochondrial Pathway-Mediated Apoptosis

BioMed Research International ◽

10.1155/2020/4929053 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Juanli Wang ◽

Hong Wu ◽

Guiting Song ◽

Donglin Yang ◽

Jiuhong Huang ◽

...

Keyword(s):

Cervical Cancer ◽

Hela Cells ◽

Mitochondrial Pathway ◽

Mitochondrial Outer Membrane ◽

Dependent Manner ◽

Mitochondrial Outer Membrane Permeabilization ◽

Cervical Cancer Cells ◽

Related Proteins ◽

Human Cervical Cancer

Background. Cancer remains a major clinical challenge because of the lack of effective drug for its treatment. To find out novel cancer chemotherapeutic molecules, we explored the anticancer effect of novel imidazopyridine compound 9i and also investigated the underlying molecular mechanism. Methods. Human cervical cancer cell (HeLa) viability was measured by an MTT assay after treatment with compound 9i. Clonogenicity of HeLa cells was investigated by an in vitro colony formation assay. Cell death was visualized by propidium iodide (PI) staining. Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and mitochondrial membrane potential in HeLa cells. The expression level of apoptosis-related proteins was also determined by western blot. Results. Compound 9i suppressed HeLa cell viability in a time- and dose-dependent manner. Compound 9i induced mitochondrial outer membrane permeabilization (MOMP), activated caspase cascade, and finally resulted in apoptosis. Conclusion. Compound 9i induces mitochondrial pathway-mediated apoptosis in human cervical cancer cells, suggesting that 9i could be a potential lead compound to be developed as a cancer therapeutic molecule.

Download Full-text