Anticancer Potential of Fruit Extracts from Vatica diospyroides Symington Type SS and Their Effect on Program Cell Death of Cervical Cancer Cell Lines

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.

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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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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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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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Propranolol Inhibits the Growth of Cervical Cancer Cells by Inhibiting Cyclic Guanosine Monophosphate/Protein Kinase G (cGMP/PKG) Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2916 ◽

2022 ◽

Vol 12 (2) ◽

pp. 422-426

Author(s):

Mi Li ◽

Yanqin Ji

Keyword(s):

Cervical Cancer ◽

Annexin V ◽

Cyclic Guanosine Monophosphate ◽

Siha Cell ◽

Guanosine Monophosphate ◽

Dependent Manner ◽

Cell Vitality ◽

Detection Assay ◽

Cervical Cancer Cells ◽

Apoptosis Detection

This study assesses the therapeutic effect of propranolol on cervical cancer and its mechanism. Propranolol’s effect on cervical cancer was evaluated by MTT, Western blotting, flow cytometry and colony formation. By searching Drug Bank and String, cGMP/PKG signaling might be downstream targets of propranolol for subsequent analysis. Our results found that propranolol could significantly inhibit Hela and SiHA cell vitality and clone formation in a dose dependent manner. Further, Annexin V-PE/7-AAD Apoptosis Detection assay showed that propranolol could increase Hela and SiHA cell apoptosis. Finally, propranolol attenuated the phosphorylation level of VASP at Ser239 which is critical for PKG activation. In conclusion, propranolol suppressed cervical cancer cell proliferation via inhibition of cGMP/PKG signaling, which provides an affordable and effective method for cervical cancer remedy.

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Leea indicaEthyl Acetate Fraction Induces Growth-Inhibitory Effect in Various Cancer Cell Lines and Apoptosis in Ca Ski Human Cervical Epidermoid Carcinoma Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2011/293060 ◽

2011 ◽

Vol 2011 ◽

pp. 1-13 ◽

Cited By ~ 7

Author(s):

Wong Yau Hsiung ◽

Habsah Abdul Kadir

Keyword(s):

Cervical Cancer ◽

Ethyl Acetate ◽

Cancer Cells ◽

Cell Lines ◽

Morphological Changes ◽

Chromatin Condensation ◽

Ethanol Extract ◽

Ethyl Acetate Fraction ◽

Cervical Cancer Cells ◽

Leea Indica

The anticancer potential ofLeea indica, a Chinese medicinal plant was investigated for the first time. The crude ethanol extract and fractions (ethyl acetate, hexane, and water) ofLeea indicawere evaluated their cytotoxicity on various cell lines (Ca Ski, MCF 7, MDA-MB-435, KB, HEP G2, WRL 68, and Vero) by MTT assay.Leea indicaethyl acetate fraction (LIEAF) was found showing the greatest cytotoxic effect against Ca Ski cervical cancer cells. Typical apoptotic morphological changes such as DNA fragmentation and chromatin condensation were observed in LIEAF-treated cells. Early signs of apoptosis such as externalization of phosphatidylserine and disruption of mitochondrial membrane potential indicated apoptosis induction. This was further substantiated by dose- and time-dependent accumulation of sub-G1cells, depletion of intracellular glutathione, and activation of caspase-3. In conclusion, these results suggested that LIEAF inhibited cervical cancer cells growth by inducing apoptosis and could be developed as potential anticancer drugs.

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Notoginsenoside R1 (NGR1) induce DNA damage to inhibit cervical cancer cells proliferation by inhibiting PHF6 activity

10.21203/rs.2.20516/v1 ◽

2020 ◽

Author(s):

Ting Cai ◽

Wenquan Wu ◽

Qiang Ming ◽

Longhua Guo ◽

Yongwu Xia ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Plasmid Vector ◽

Panax Notoginseng ◽

S Phase ◽

Dependent Manner ◽

Edible Plant ◽

Over Expression ◽

Cervical Cancer Cells ◽

Dose Dependent

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.

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Cytotoxic Effect and Induction of Apoptosis in Human Cervical Cancer Cells by Antrodia camphorata

The American Journal of Chinese Medicine ◽

10.1142/s0192415x13500791 ◽

2013 ◽

Vol 41 (05) ◽

pp. 1169-1180 ◽

Cited By ~ 8

Author(s):

Pei-Yu Yang ◽

Dan-Ning Hu ◽

Fu-Shing Liu

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Chinese Herb ◽

Dependent Manner ◽

Chromosomal Dna ◽

Antrodia Camphorata ◽

Cervical Cancer Cells ◽

Human Cervical Cancer

Antrodia camphorata is a Chinese herb indigenous to Taiwan. Previous reports demonstrated that it could induce apoptosis in some cancer cells. The purpose of this study was to investigate the apoptotic effect of the crude extract of A. camphorata in cervical cancer cells. Two human cervical cancer cell lines, HeLa and C-33A, were treated with extract of A. camphorata (10–1000 μg/mL). We found that A. camphorata extract was cytotoxic to both cervical cancer cells in a dose- and time-dependent manner as examined by MTT assay. Treatment with A. camphorata extract at 400 μg/mL induced a 2.3- and 4.4-fold increase in oligonucleosome formation from the cleaved chromosomal DNA in HeLa and C-33A cells, respectively. A. camphorata extract also activated caspase-3, -8, and -9 activities and increased the cytosolic level of cytochrome c in both cell lines as the dosage increased. Furthermore, A. camphorata extract increased expressions of Bak, Bad and Bim, while decreasing expressions of Bcl-2 and Bcl-xL of the Bcl-2 family proteins in HeLa and C-33A cells. The expression of IAP proteins, XIAP and survivin, was also decreased in both cervical cancer cells after treatment with A. camphorata. Our in vitro study suggests that A. camphorata is cytotoxic to cervical cancer cells through both extrinsic and intrinsic apoptotic mechanisms. It could be used as a novel phytotherapeutic agent or auxiliary therapy in the treatment of 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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Cytotoxic Effect of Disulfiram/Copper On Human Cervical Cancer Cell Lines and LGR5-Positive Cancer Stem-Like Cells

10.21203/rs.3.rs-1122434/v1 ◽

2021 ◽

Author(s):

Hao-Zhe Cao ◽

Peng-Sheng Zheng ◽

Wen-Ting Yang

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Mtt Assay ◽

Cancer Cell Lines ◽

Cervical Cancer Cell ◽

Dependent Manner ◽

Cu Complex ◽

Cervical Cancer Cells

Abstract Background: Tumor resistance is a global challenge for tumor treatment. Cancer stem cells (CSCs) are the main population of tumor cells for drug resistance. We have reported that high aldehyde dehydrogenase (ALDH) activity represents a functional marker for cervical CSCs. Here we aim at disulfiram (DS), an ALDH inhibitor, that has the potential as a novel treatment to be used for cervical cancer.Methods: MTT assay, western blot, FCS analysis and sorting, vector construction and transfection, in vivo anti-tumor assays were performed using cervical cancer cell lines SiHa and HeLa. Cell cycle distribution and cell apoptosis were carried out by flow cytometry. The cytotoxicity of DS was detected by MTT assay and a xenograft cervical cancer model. Results: Disulfiram was cytotoxic to cervical cancer cell lines in a copper (Cu)-dependent manner. Disulfiram/copper (DS/Cu) complex induced deregulation of S-phase and inhibited the expression of stemness marker in cervical cancer cells. DS/Cu caused the death of LGR5-positive cervical cancer cells, a cancer stem-like cell population, which lead to cisplatin resistance in cervical cancer cells. Furthermore, DS/Cu complex had the greater antitumor efficacy on cervical cancer than cisplatin group in vitro and in vivo. Conclusion: Our findings indicate that the cytotoxicity of DS/Cu complex may be superior to cisplatin because of targeting LGR5-positive cervical cancer stem-like cells in cervical cancer. Thus, the DS/Cu complex may represent a potential therapeutic strategy for cervical cancer patients.

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Adenoviral Vectors Armed with PAPILLOMAVIRUs Oncogene Specific CRISPR/Cas9 Kill Human-Papillomavirus-Induced Cervical Cancer Cells

Cancers ◽

10.3390/cancers12071934 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1934 ◽

Cited By ~ 1

Author(s):

Eric Ehrke-Schulz ◽

Sonja Heinemann ◽

Lukas Schulte ◽

Maren Schiwon ◽

Anja Ehrhardt

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Adenoviral Vectors ◽

Human Papillomaviruses ◽

Cervical Cancer Cell ◽

Adenoviral Delivery ◽

Cervical Cancer Cells

Human papillomaviruses (HPV) cause malignant epithelial cancers including cervical carcinoma, non-melanoma skin and head and neck cancer. They drive tumor development through the expression of their oncoproteins E6 and E7. Designer nucleases were shown to be efficient to specifically destroy HPV16 and HPV18 oncogenes to induce cell cycle arrest and apoptosis. Here, we used high-capacity adenoviral vectors (HCAdVs) expressing the complete CRISPR/Cas9 machinery specific for HPV18-E6 or HPV16-E6. Cervical cancer cell lines SiHa and CaSki containing HPV16 and HeLa cells containing HPV18 genomes integrated into the cellular genome, as well as HPV-negative cancer cells were transduced with HPV-type-specific CRISPR-HCAdV. Upon adenoviral delivery, the expression of HPV-type-specific CRISPR/Cas9 resulted in decreased cell viability of HPV-positive cervical cancer cell lines, whereas HPV-negative cells were unaffected. Transduced cervical cancer cells showed increased apoptosis induction and decreased proliferation compared to untreated or HPV negative control cells. This suggests that HCAdV can serve as HPV-specific cancer gene therapeutic agents when armed with HPV-type-specific CRISPR/Cas9. Based on the versatility of the CRISPR/Cas9 system, we anticipate that our approach can contribute to personalized treatment options specific for the respective HPV type present in each individual tumor.

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