scholarly journals c-Jun N-terminal Kinase Inhibitor II (SP600125) Activates Müllerian Inhibiting Substance Type II Receptor-Mediated Signal Transduction

Endocrinology ◽  
2007 ◽  
Vol 149 (1) ◽  
pp. 108-115 ◽  
Author(s):  
Nina Renlund ◽  
Rafael Pieretti-Vanmarcke ◽  
Francis H. O’Neill ◽  
LiHua Zhang ◽  
Patricia K. Donahoe ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Signal Transduction ◽  
Cancer Cells ◽  
Kinase Inhibitor ◽  
Therapeutic Potential ◽  
Physiological Role ◽  
Recurrent Ovarian Cancer ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Type Ii

Müllerian inhibiting substance (MIS), the hormone required for Müllerian duct regression in fetal males, is also expressed in both adult males and females, but its physiological role in these settings is not clear. The expression of the MIS type II receptor (MISRII) in ovarian cancer cells and the ability of MIS to inhibit proliferation of these cells suggest that MIS might be a promising therapeutic for recurrent ovarian cancer. Using an MISRII-dependent activity assay in a small-molecule screen for MIS-mimetic compounds, we have identified the c-Jun N-terminal kinase inhibitor SP600125 as an activator of the MIS signal transduction pathway. SP600125 increased the activity of a bone morphogenetic protein-responsive reporter gene in a dose-dependent manner and exerted a synergistic effect when used in combination with MIS. This effect was specific for the MISRII and was not seen with other receptors of the TGFβ family. Moreover, treatment of mouse ovarian cancer cells with a combination of SP600125 and paclitaxel, an established chemotherapeutic agent used in the treatment of ovarian cancer, or with MIS enabled inhibition of cell proliferation at a lower dose than with each treatment alone. These results offer a strong rationale for testing the therapeutic potential of SP600125, alone or in combination with already established drugs, in the treatment of recurrent ovarian cancer with a much-needed decrease in the toxic side effects of currently employed therapeutic agents.

scholarly journals Piperlongumine Induces Apoptosis and Synergizes with Cisplatin or Paclitaxel in Human Ovarian Cancer Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Li-Hua Gong ◽  
Xiu-Xiu Chen ◽  
Huan Wang ◽  
Qi-Wei Jiang ◽  
Shi-Shi Pan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Therapeutic Potential ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Dependent Manner ◽  
Ros Accumulation ◽  
M Phase ◽  
Natural Alkaloid

Piperlongumine (PL), a natural alkaloid fromPiper longum L., possesses the highly selective and effective anticancer property. However, the effect of PL on ovarian cancer cells is still unknown. In this study, we firstly demonstrate that PL selectively inhibited cell growth of human ovarian cancer cells. Furthermore, PL notably induced cell apoptosis, G2/M phase arrest, and accumulation of the intracellular reactive oxidative species (ROS) in a dose- and time-dependent manner. Pretreatment with antioxidant N-acety-L-cysteine could totally reverse the PL-induced ROS accumulation and cell apoptosis. In addition, low dose of PL/cisplatin or paclitaxel combination therapies had a synergistic antigrowth effect on human ovarian cancer cells. Collectively, our study provides new therapeutic potential of PL on human ovarian cancer.

scholarly journals Gamma secretase inhibitors inhibit ovarian cancer development and enhance olaparib’s anti-ovarian cancer activity and its mechanism

2020 ◽  
Author(s):  
Yao Xiaoxiao ◽  
Zheng Nan
Keyword(s):  
Ovarian Cancer ◽  
Signal Transduction ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Tumor Development ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Secretase Inhibitor ◽  
Combination Drugs ◽  
Cancer Activity

AbstractBackgroundOvarian cancer is the fifth leading cause of cancer-related deaths in women. Although cytoreductive surgery combined with chemotherapy and / or targeted therapy has achieved a certain effect, but advanced patients have limited clinical benefits and are prone to relapse. Among them, Notch / jagged1 and Wnt / β-catenin signal transduction plays an important role in the development of ovarian cancer and chemotherapy resistance, and it is very important to find new effective therapeutic drugs to inhibit tumor development and increase tumor chemotherapy sensitivity.MethodsTo establish ovarian cancer xenotransplantation model, to detect the effects of γ-secretase inhibitor, olaparib and combination drugs on the development of ovarian cancer, and to detect the proliferation and apoptosis of ovarian cancer cells with γ-secretase inhibitor, olaparib and combination drugs .After knocking down Jagged1 or β-catenin, the protein expression levels of related signaling pathways under different drug treatments were analyzed by immunoblotting, and related gene expression changes were analyzed.ResultsDAPT reduced β-catenin expression in a proteasome-synthetic pathway-dependent manner, thereby inhibiting the synthesis and transcription of Jagged1 protein, thereby inhibiting the expression of Notch signal transduction pathway-related proteins and gene transcription, inhibiting the activity of ovarian cancer cells and inducing cell apoptosis death, enhance the anti-ovarian cancer activity of olaparib.ConclusionDAPT inhibits cell proliferation, induces cell apoptosis, inhibits tumor development in vivo through β-catenin / Jagged1 inhibition, and exerts anti-ovarian cancer activity sensitizing effect of olaparib.

scholarly journals Propofol suppresses cell viability, cell cycle progression and motility and induces cell apoptosis of ovarian cancer cells through suppressing MEK/ERK signaling via targeting circVPS13C/miR-145 axis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Huan Lu ◽  
Guanlin Zheng ◽  
Xiang Gao ◽  
Chanjuan Chen ◽  
Min Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Rna Binding ◽  
Erk Signaling ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Vacuolar Protein

Abstract Background Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. Methods The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. Results Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. Conclusion Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro.

scholarly journals Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1711
Author(s):  
Michelle Bilbao ◽  
Chelsea Katz ◽  
Stephanie L. Kass ◽  
Devon Smith ◽  
Krystal Hunter ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
3D Culture ◽  
Extended Period ◽  
Recurrent Ovarian Cancer ◽  
Epigenetic Therapy ◽  
Ovarian Cancer Cells ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Cancer Spheroids

Recurrent high-grade serous ovarian cancer (HGSC) is clinically very challenging and prematurely shortens patients’ lives. Recurrent ovarian cancer is characterized by high tumor heterogeneity; therefore, it is susceptible to epigenetic therapy in classic 2D tissue culture and rodent models. Unfortunately, this success has not translated well into clinical trials. Utilizing a 3D spheroid model over a period of weeks, we were able to compare the efficacy of classic chemotherapy and epigenetic therapy on recurrent ovarian cancer cells. Unexpectedly, in our model, a single dose of paclitaxel alone caused the exponential growth of recurrent high-grade serous epithelial ovarian cancer over a period of weeks. In contrast, this effect is not only opposite under treatment with panobinostat, but panobinostat reverses the repopulation of cancer cells following paclitaxel treatment. In our model, we also demonstrate differences in the drug-treatment sensitivity of classic chemotherapy and epigenetic therapy. Moreover, 3D-derived ovarian cancer cells demonstrate induced proliferation, migration, invasion, cancer colony formation and chemoresistance properties after just a single exposure to classic chemotherapy. To the best of our knowledge, this is the first evidence demonstrating a critical contrast between short and prolonged post-treatment outcomes following classic chemotherapy and epigenetic therapy in recurrent high-grade serous ovarian cancer in 3D culture.

Redox resetting of cisplatin-resistant ovarian cancer cells by cisplatin-encapsulated nanostructured lipid carriers

Nanomedicine ◽  
2021 ◽  
Author(s):  
Disha Mittal ◽  
Largee Biswas ◽  
Anita Kamra Verma
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Therapeutic Potential ◽  
Nanostructured Lipid Carriers ◽  
Ovarian Cancer Cells ◽  
Oxygen Species ◽  
X Ray Diffraction ◽  
X Ray ◽  
Resistance Markers ◽  
Fourier Transform Ir

Aim: To sensitize cisplatin (Cis)-resistant ovarian cancer cells toward Cis using Cis-loaded nanostructured lipid carriers (CisNLCs). Materials & methods: CisNLCs were synthesized and characterized using dynamic light scattering, Fourier transform IR and x-ray diffraction (XRD). Sensitivity of PA-1 and CaOV3 cells to Cis and its biotoxicity were assessed. Further, expression of the Cis-resistance markers GSTPi and  ATP7B, and apoptotic markers Bax, Bcl2 and Cas9 were quantified by real-time PCR. Results: The size of synthesized CisNLCs was approximately 179.3 ± 2.32 nm and surface charge was -33.9 ± 1.47 mV. IC50 was 210 μg/ml in PA-1 and 500 μg/ml in CaOV3. CisNLCs modulated reactive oxygen species levels in CaOV3 cells. Reduced GSTPi and decreased Cis efflux via ATP7B sequestration caused Cis to accumulate in cytoplasm, thereby augmenting apoptosis in cells. Conclusion: CisNLCs sensitize CaOV3 by redox resetting, indicating their immense therapeutic potential.

224 A GROWTH OF HUMAN BG-1 CANCER CELLS EXPRESSING ESTROGEN RECEPTORS WAS ENHANCED BY SYNTHETIC PYRETHROIDS, LAMBDA-CYHALOTHRIN AND CYPERMETHRIN, VIA AN ESTROGEN RECEPTOR-DEPENDENT SIGNALING PATHWAY

2015 ◽  
Vol 27 (1) ◽  
pp. 201 ◽  
Author(s):  
C.-W. Kim ◽  
R.-E. Go ◽  
K.-C. Choi
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Mtt Assay ◽  
Ovarian Cancer Cells ◽  
Transcriptional Level ◽  
Synthetic Pyrethroids ◽  
Dependent Manner ◽  
Rt Pcr ◽  
Pyrethroid Insecticides ◽  
Lambda Cyhalothrin

Synthetic pyrethroids (SP) are the most common pesticides in recent use, which are used as indoor pest control. The widespread use of SPs has resulted in extensive exposure to wildlife and human. Recently some SPs are suspected as endocrine disrupting chemicals (EDC) and have been assessed for their potential estrogenicity by various assays. In this study, we examined the estrogenic effects of lambda-cyhalothrin (LCT) and cypermethrin (CP), the most commonly used pyrethroid insecticides in Korea, using BG-1 ovarian cancer cells expressing oestrogen receptors (ER). To evaluate the estrogenic activities of two SPs, LCT and CP, we employed MTT assay and reverse-transcription polymerase chain reaction (RT–PCR). In MTT assay, LCT (10–6 M) and CP (10–5 M) significantly induced the growth of BG-1 cancer cells, 1.61 ± 0.1 and 1.45 ± 0.06 times, respectively, as 17β-oestradiol (E2, 10–9 M, 2.73 ± 0.25 times) did. LCT or CP-induced cell growth was reversed to a control level (DMSO) by addition of ICI 182 720 (10–8 M), an ER antagonist, suggesting that this effect appears to be mediated by an ER-dependent manner. Moreover, RT–PCR results showed that transcriptional level of ERα expression was significantly down-regulated by LCT and CP as in case of E2. Taken together, these results indicate that LCT and CP may possess estrogenic potentials to stimulate ovarian cancer cells expressing ERs via an ER-dependent manner, and these collective results confirm the carcinogenicity of these SP, LCT and CP, in ER-positive cells or tissues.

Mechanism of Cepharanthine Cytotoxicity in Human Ovarian Cancer Cells

Planta Medica ◽  
2018 ◽  
Vol 85 (01) ◽  
pp. 41-47 ◽  
Author(s):  
Vilawan Payon ◽  
Chanaporn Kongsaden ◽  
Wannarasmi Ketchart ◽  
Apiwat Mutirangura ◽  
Piyanuch Wonganan
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cell ◽  
Apoptotic Cell ◽  
Chemotherapeutic Agents ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ovarian Cancer Cell Lines ◽  
Underlying Mechanisms

AbstractCepharanthine (CEP), a medicinal product derived from Stephania cephalantha Hayata, possesses a potent cytotoxicity against several types of cancers. Recently, we have found that CEP could efficiently inhibit the growth of mutated p53 colon cancer cells, which are often resistant to commonly used chemotherapeutic agents. In this study, we evaluated the cytotoxic effect and the underlying mechanisms of CEP on both chemosensitive CaOV-3 and chemoresistant OVCAR-3 ovarian cancer cell lines. The present study demonstrated that CEP significantly inhibited the growth of CaOV-3 and OVCAR-3 cells in a time- and concentration-dependent manner. CEP arrested CaOV-3 and OVCAR-3 cells in the G1 phase and S phase of cell cycle, respectively. Western blot analysis demonstrated that CEP markedly increased the expression of p21Waf1 protein and decreased the expression of cyclins A and D proteins in both CaOV-3 and OVCAR-3 cells. Additionally, CEP triggered apoptotic cell death in OVCAR-3 cells. Taken together, the above results suggest that CEP is a promising anticancer drug for ovarian cancer.

scholarly journals Aurora-A induces cell survival and chemoresistance by activation of Akt through a p53-dependent manner in ovarian cancer cells

2006 ◽  
Vol 119 (10) ◽  
pp. 2304-2312 ◽  
Author(s):  
Hua Yang ◽  
Lili He ◽  
Patricia Kruk ◽  
Santo V. Nicosia ◽  
Jin Q. Cheng
Keyword(s):  
Ovarian Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Aurora A

scholarly journals Triptolide Transcriptionally Represses HER2 in Ovarian Cancer Cells by Targeting NF-κB

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Chien-Chih Ou ◽  
Yuan-Wu Chen ◽  
Shih-Chung Hsu ◽  
Huey-Kang Sytwu ◽  
Shih-Hurng Loh ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Protein Expression ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Promoter Activity ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Ki 67 ◽  
Nih3t3 Cells ◽  
Her2 Protein

Triptolide (TPL) inhibits the proliferation of a variety of cancer cells and has been proposed as an effective anticancer agent. In this study, we demonstrate that TPL downregulates HER2 protein expression in oral, ovarian, and breast cancer cells. It suppresses HER2 protein expression in a dose- and time-dependent manner. Transrepression of HER2 promoter activity by TPL is also observed. The interacting site of TPL on the HER2 promoter region is located between −207 and −103 bps, which includes a putative binding site for the transcription factor NF-κB. Previous reports demonstrated that TPL suppresses NF-κB expression. We demonstrate that overexpression of NF-κB rescues TPL-mediated suppression of HER2 promoter activity and protein expression in NIH3T3 cells and ovarian cancer cells, respectively. In addition, TPL downregulates the activated (phosphorylated) forms of HER2, phosphoinositide-3 kinase (PI3K), and serine/threonine-specific protein kinase (Akt). TPL also inhibits tumor growth in a mouse model. Furthermore, TPL suppresses HER2 and Ki-67 expression in xenografted tumors based on an immunohistochemistry (IHC) assay. These findings suggest that TPL transrepresses HER2 and suppresses the downstream PI3K/Akt-signaling pathway. Our study reveals that TPL can inhibit tumor growth and thereby may serve as a potential chemotherapeutic agent.

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