scholarly journals Saponins Extracted from Tea (Camellia Sinensis) Flowers Induces Autophagy in Ovarian Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5254
Author(s):  
Yaomin Wang ◽  
Chen Xia ◽  
Lianfu Chen ◽  
Yi Charlie Chen ◽  
Youying Tu
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Ros Generation ◽  
Preparative Hplc ◽  
Protein Levels ◽  
Anticancer Properties ◽  
Extraction And Purification ◽  
Pathway Activation ◽  
Resin Separation

Tea flower saponins (TFS) possess effective anticancer properties. The diversity and complexity of TFS increases the difficulty of their extraction and purification from tea flowers. Here, multiple methods including solvent extraction, microporous resin separation and preparative HPLC separation were used to obtain TFS with a yield of 0.34%. Furthermore, we revealed that TFS induced autophagy—as evidenced by an increase in MDC-positive cell populations and mCherry-LC3B-labeled autolysosomes and an upregulation of LC3II protein levels. 3-MA reversed the decrease in cell viability induced by TFS, showing that TFS induced autophagic cell death. TFS-induced autophagy was not dependent on the Akt/mTOR/p70S6K signaling pathway. TFS-induced autophagy in OVCAR-3 cells was accompanied by ERK pathway activation and reactive oxygen species (ROS) generation. This paper is the first report of TFS-mediated autophagy of ovarian cancer cells. These results provide new insights for future studies of the anti-cancer effects of TFS.

scholarly journals Dasatinib (BMS-35482) Interacts Synergistically With Docetaxel, Gemcitabine, Topotecan, and Doxorubicin in Ovarian Cancer Cells With High SRC Pathway Activation and Protein Expression

2014 ◽  
Vol 24 (2) ◽  
pp. 218-225 ◽  
Author(s):  
Angeles Alvarez Secord ◽  
Deanna Teoh ◽  
Jingquan Jia ◽  
Andrew B. Nixon ◽  
Lisa Grace ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Combination Index ◽  
Chemotherapeutic Agents ◽  
Cytotoxic Agents ◽  
Ovarian Cancer Cells ◽  
Response Curves ◽  
Pathway Activation ◽  
Skov3 Cells

PurposeThis study aimed to explore the activity of dasatinib in combination with docetaxel, gemcitabine, topotecan, and doxorubicin in ovarian cancer cells.MethodsCells with previously determined SRC pathway and protein expression (SRC pathway/SRC protein IGROV1, both high; SKOV3, both low) were treated with dasatinib in combination with the cytotoxic agents. SRC and paxillin protein expression were determined pretreatment and posttreatment. Dose-response curves were constructed, and the combination index (CI) for drug interaction was calculated.ResultsIn the IGROV1 cells, dasatinib alone reduced phospho-SRC/total SRC 71% and p-paxillin/t-paxillin ratios 77%. Phospho-SRC (3%–33%; P = 0.002 to 0.04) and p-paxicillin (6%–19%; P = 0.01 to 0.05) levels were significantly reduced with dasatinib in combination with each cytotoxic agent. The combination of dasatinib and docetaxel, gemcitabine, or topotecan had a synergistic antiproliferative effect (CI, 0.49–0.68), whereas dasatinib combined with doxorubicin had an additive effect (CI, 1.08).In SKOV3 cells, dasatinib resulted in less pronounced reductions of phospho-SRC/total SRC (49%) and p-paxillin/t-paxillin (62%). Phospho-SRC (18%; P < 0.001) and p-paxillin levels (18%; P = 0.001; 9%; P = 0.007) were significantly decreased when dasatinib was combined with docetaxel and topotecan (p-paxillin only). Furthermore, dasatinib combined with the cytotoxics in the SKOV3 cells produced an antagonistic interaction on the proliferation of these cells (CI, 1.49–2.27).ConclusionsDasatinib in combination with relapse chemotherapeutic agents seems to interact in a synergistic or additive manner in cells with high SRC pathway activation and protein expression. Further evaluation of dasatinib in combination with chemotherapy in ovarian cancer animal models and exploration of the use of biomarkers to direct therapy are warranted.

scholarly journals Fucosterol Suppresses the Progression of Human Ovarian Cancer by Inducing Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

Marine Drugs ◽  
2020 ◽  
Vol 18 (5) ◽  
pp. 261 ◽  
Author(s):  
Hyocheol Bae ◽  
Jin-Young Lee ◽  
Gwonhwa Song ◽  
Whasun Lim
Keyword(s):  
Ovarian Cancer ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Xenograft Model ◽  
Tumor Formation ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Anticancer Properties

Ovarian cancer is difficult to diagnose early and has high rates of relapse and mortality. Therefore, the treatment of ovarian cancer needs to be improved. Recently, several studies have been conducted in an attempt to develop anticancer drugs from naturally derived ingredients. Compared to traditional chemotherapy, natural compounds can overcome drug resistance with lower side effects. Fucosterol, a phytosterol present in brown algae, reportedly possesses many bioactive effects, including anticancer properties. However, the anticancer effects of fucosterol in ovarian cancer remain unexplored. Therefore, we investigated the effects of fucosterol on progression in human ovarian cancer cells. Fucosterol inhibited cell proliferation and cell-cycle progression in ovarian cancer cells. Additionally, fucosterol regulated the proliferation-related signaling pathways, the production of reactive oxygen species, mitochondrial function, endoplasmic reticulum stress, angiogenesis, and calcium homeostasis. Moreover, it decreased tumor formation in a zebrafish xenograft model. These results indicate that fucosterol could be used as a potential therapeutic agent in ovarian cancer.

scholarly journals Difluoromethylornithine Induces Apoptosis through Regulation of AP-1 Signaling via JNK Phosphorylation in Epithelial Ovarian Cancer

2021 ◽  
Vol 22 (19) ◽  
pp. 10255
Author(s):  
Woo Yeon Hwang ◽  
Wook Ha Park ◽  
Dong Hoon Suh ◽  
Kidong Kim ◽  
Yong Beom Kim ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Irreversible Inhibitor ◽  
Protein Levels ◽  
Bax Protein ◽  
Apoptotic Effects

Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), has promising activity against various cancers and a tolerable safety profile for long-term use as a chemopreventive agent. However, the anti-tumor effects of DFMO in ovarian cancer cells have not been entirely understood. Our study aimed to identify the effects and mechanism of DFMO in epithelial ovarian cancer cells using SKOV-3 cells. Treatment with DFMO resulted in a significantly reduced cell viability in a time- and dose-dependent manner. DFMO treatment inhibited the activity and downregulated the expression of ODC in ovarian cancer cells. The reduction in cell viability was reversed using polyamines, suggesting that polyamine depletion plays an important role in the anti-tumor activity of DFMO. Additionally, significant changes in Bcl-2, Bcl-xL, Bax protein levels, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase were observed, indicating the apoptotic effects of DFMO. We also found that the effect of DFMO was mediated by AP-1 through the activation of upstream JNK via phosphorylation. Moreover, DFMO enhanced the effect of cisplatin, thus showing a possibility of a synergistic effect in treatment. In conclusion, treatment with DFMO alone, or in combination with cisplatin, could be a promising treatment for ovarian cancer.

Cytotoxic Activity of Gallic Acid and Myricetin against Ovarian Cancer Cells by Production of Reactive Oxygen Species

2021 ◽  
Vol 7 (1) ◽  
pp. 7
Author(s):  
Luis Varela-Rodríguez ◽  
Patricia Talamás-Rohana ◽  
Blanca Sánchez-Ramírez ◽  
Verónica Ivonne Hernández-Ramírez ◽  
Hugo Varela-Rodríguez
Keyword(s):  
Ovarian Cancer ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Gallic Acid ◽  
Therapeutic Potential ◽  
Chromatin Condensation ◽  
Vehicle Group ◽  
Ovarian Cancer Cells ◽  
Ros Generation ◽  
In Silico Studies

Some studies demonstrate that gallic acid (GA) and myricetin (MYR) isolated from Rhus trilobata provide the therapeutic activity of this plant against cancer. However, few reports demonstrate that both compounds could also have therapeutic potential in ovarian cancer. Therefore, evaluating the cytotoxic activity of GA and MYR against ovarian cancer cells and determining the possible action mechanism present are important. For this purpose, SKOV-3 cells (ovarian adenocarcinoma; HTB-77™, ATCC®) were cultivated according to the supplier’s instructions (37 °C and 5% CO2) to determine the biological activity of GA and MYR by confocal/transmission electron microscopy, PI-flow cytometry, H2DCF-DA, MTT, and Annexin-V assays. Possible molecular targets of the compounds were determined by the Similarity Ensemble approach. Results showed that GA and MYR treatments decreased the viability of SKOV-3 cells at 50 and 166 μg/mL, respectively (p ≤ 0.05, ANOVA vs. vehicle group). They also induced morphological changes (cytoplasmic reduction, nuclear chromatin condensation, cytoplasmic vesicles increment, polymerized actin, and stabilized tubulin), cell cycle arrest (GA: 8.3% G2/M and MYR: 78% G1), and apoptosis induction (GA: 18.9% and MYR: 8.1%), due to ROS generation (34 to 42%) for 24 h (p ≤ 0.05, ANOVA vs. vehicle group). In silico studies demonstrated that GA and MYR interact with carbonic anhydrase-IX and PI3K, respectively. In conclusion, GA and MYR show cytotoxic activity against SKOV-3 cells through ROS production, which modifies the cytoskeleton and induces apoptosis. Therefore, GA and MYR could be considered as base compounds for the development of new treatments in chemotherapy for ovarian cancer.

HPIP promotes epithelial-mesenchymal transition and cisplatin resistance in ovarian cancer cells through PI3K/AKT pathway activation

2016 ◽  
Vol 40 (2) ◽  
pp. 133-144 ◽  
Author(s):  
Suresh Bugide ◽  
Vijay Kumar Gonugunta ◽  
Vasudevarao Penugurti ◽  
Vijaya Lakshmi Malisetty ◽  
Ratna K. Vadlamudi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Epithelial Mesenchymal Transition ◽  
Akt Pathway ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Pathway Activation

scholarly journals ADAR1 Prevents R-loop Accumulation-Driven ATR Pathway Activation in Ovarian Cancer

2020 ◽  
Author(s):  
hanwei cui ◽  
Qian Yi ◽  
Min Tian ◽  
Yuteng Liang ◽  
Jie Huang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Pathway Activation ◽  
Rna Immunoprecipitation ◽  
Cancer Tissues

Abstract BackgroundAdenosine (A)-to-inosine (I) RNA editing is the most prevalent RNA editing mechanism, in which adenosine deaminases acting on RNA 1 (ADAR1) is a major adenosine deaminase. Increasing evidence suggests that editing dysregulation of ADAR1 plays an important role in human tumorigenesis, while the underlying mechanism remains elusive. MethodsThe clinical relevance of ADAR1 was analyzed by real-time PCR, western blotting and immunohistochemistry of ovarian cancer tissues. ADAR1 function on ovarian cancer cells in vitro were explored by colony formation assay, transwell assay and Brdu-based cell cycle assay in vitro and xenograft models in vivo. Western blotting, immunostaining and DNA/RNA immunoprecipitation-qPCR were conducted to confirm DNA damage and R-loop accumulation in ovarian cancer cells. Co-immunoprecipitation and DNA/RNA immunoprecipitation were performed to detect interaction of DHX9, ADAR1 and R-loop complex in ovarian cancer cells.ResultsWe demonstrated that ADAR1 was highly expressed in ovarian cancer tissues and negatively correlated with progression free survival of ovarian cancer patients. Importantly, silence of ADAR1 repressed ovarian cancer cell growth and colony formation in vitro and inhibited ovarian cancer cell tumorigenesis in vivo. Further cell cycle and transcriptome profile analysis revealed that silence of ADAR1 in ovarian cancer cells induced cell cycle arrest at G1/G0 stage. Mechanically, loss of ADAR1 caused R-loop abnormal accumulation, thereby contributing to single stand DNA break and ATR pathway activation. Additionally, ADAR1 interacted with DHX9 to regulate R-loop complex formation, and A-to-I editing of nascent RNA repressed R-loop formation during co-transcriptional process. ConclusionsOur results identify a novel ADAR1/R-loop/ATR axis critical for ovarian cancer progression and a potential target for ovarian cancer therapy.

scholarly journals Poly-amino acids coated gold nanorod and doxorubicin for synergistic photodynamic therapy and chemotherapy in ovarian cancer cells

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
JinYing Liu ◽  
Wei Ma ◽  
Wei Kou ◽  
Lina Shang ◽  
Rui Huang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Photothermal Therapy ◽  
Near Infrared ◽  
Malignant Tumors ◽  
Gold Nanorod ◽  
Cell Group ◽  
Ovarian Cancer Cells ◽  
Ros Generation ◽  
Burst Release

Abstract In this work, we have successfully designed and formulated a doxorubicin-loaded polypeptide-based multilayer assembled gold nanorod (DH-GNR). We have hypothesized that near-infrared (NIR) laser irradiation of DH-GNR will combine the benefits of chemotherapy and photothermal therapy. The GNR was surface functionalized with poly-glutamic acid (PGA) and poly-l-Lysine (PLL) with a final layer of hyaluronic acid (HA) that could also serve as a targeting ligand toward the overexpressed CD44 receptors in ovarian cancer cells. The zigzag ζ potential of nanoparticle is a proof of successful assembly of alternative polymers on the GNR surface. NIR irradiation exhibited a burst release of drug in pH 7.4 and pH 5.0 buffer conditions. The combination of doxorubicin (DOX)-based chemotherapy and GNR-based photothermal therapy exhibited a synergistic effect in killing the SKOV3 cancer cells. DH-GNR(+NIR) induced a 82.5% apoptosis (combined early and late apoptosis) compared with only 35.2 and 38.5% for DOX or DH-GNR(−NIR) treated cell group. Results clearly suggest that the excessive reactive oxygen species (ROS) generation in DH-GNR (+NIR) might be responsible for the cell apoptosis and cell death. The promising anticancer effect of DH-GNR will be of great potential in the treatment of ovarian cancers and worth further development for treating other malignant tumors.

Aloperine Induces Apoptosis by a Reactive Oxygen Species Activation Mechanism in Human Ovarian Cancer Cells

2020 ◽  
Vol 27 (9) ◽  
pp. 860-869 ◽  
Author(s):  
Mingning Qiu ◽  
Jie Liu ◽  
Yongxia Su ◽  
Jianjun Liu ◽  
Chenchen Wu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Ovarian Cancer ◽  
Hydrogen Peroxide ◽  
Cell Viability ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Activation Mechanism ◽  
Ovarian Cancer Cells ◽  
Ros Generation ◽  
Oxygen Species

Background: Ovarian cancer is the most lethal gynecologic malignancy worldwide with poor prognosis owing to chemotherapy resistance and cancer relapse. Hence, there is an urgent need to develop novel anticancer agents against ovarian cancer. Objective: The aim of this research is to investigate the possible anticancer activity of aloperine, an active ingredient from a traditional Chinese medicine Sophora alopecuroides, and to explore the possible Reactive Oxygen Species (ROS)-related mechanism. Methods: Cell viability, cytotoxicity, apoptosis, ROS generation, and oxidant stress indicators were analyzed. Results: Our results demonstrated that aloperine significantly induced inhibition of cell viability, promoted cytotoxicity and mitochondrial-related apoptosis, and increased ROS generation in ovarian cancer cells. Furthermore, the antioxidant α-lipoic acid reversed apoptosis in aloperinetreated cells. In addition, we identified hydrogen peroxide as the main type of ROS, and the antioxidant catalase suppressed the apoptotic inducing effect of aloperine whereas hydrogen peroxide supplement exacerbated the effect of aloperine in ovarian cancer cells. Conclusion: Taken together, our results indicated that aloperine could exert anti-ovarian cancer cell activity through a reactive oxygen species activation mechanism and suggested aloperine as a potential agent against ovarian cancer.

scholarly journals The Impact of Integrin-Mediated Matrix Adhesion on Cisplatin Resistance of W1 Ovarian Cancer Cells

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 788 ◽  
Author(s):  
Kathleen Wantoch von Rekowski ◽  
Philipp König ◽  
Svenja Henze ◽  
Martin Schlesinger ◽  
Piotr Zawierucha ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Genetic Resistance ◽  
Collagen Type I ◽  
Ovarian Cancer Cells ◽  
Type I ◽  
Mrna Levels ◽  
Protein Levels ◽  
The Impact

Background: Tumor cell binding to the microenvironment is regarded as the onset of therapeutic resistance, referred to as cell adhesion mediated drug resistance (CAM-DR). Here we elucidate whether CAM-DR occurs in ovarian cancer cells and contributes to still-existing cisplatin resistance. Methods: Cultivation of W1 and cisplatin-resistant W1CR human ovarian cancer cells on collagen-type I (COL1) was followed by whole genome arrays, MTT assays focusing cisplatin cytotoxicity, and AAS detection of intracellular platinum levels. Expression of cisplatin transporters Ctr1 and MRP2 was analyzed. Mechanistic insight was provided by lentiviral β1-integrin (ITGB1) knockdown, or inhibition of integrin-linked kinase (ILK). Results: EC50 values of cisplatin cytotoxicity increased twofold when W1 and W1CR cells were cultivated on COL1, associated with significantly diminished intracellular platinum levels. Transporter deregulation could not be detected at mRNA levels but appears partially responsible at protein levels. The ITGB1 knockdown confirms that CAM-DR follows a COL1/ITGB1 signaling axis in W1 cells; thus, a blockade of ILK re-sensitized W1 cells on COL1 for cisplatin. In contrast, CAM-DR adds to cisplatin resistance in W1CR cells independent of ITGB1. Conclusions: CAM-DR appears relevant for ovarian cancer cells, adding to existing genetic resistance and thus emerges as a target for sensitization strategies.

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