Dual Effects of Omega -6, and -9 Fatty Acids on Ovarian Cancer Cell Viability and Their Ability to Induce Apoptosis

ObjectiveThe current preferred treatment of ovarian cancer is combination chemotherapy, usually a platinum-based drug coupled with paclitaxel (PTX). Here, we investigated whether co-treatment with valproic acid (VPA) could increase the efficiency of various ovarian cancer drugs—PTX, doxorubicin (DOX), carboplatin (CBP), and cyclophosphamide (CP)—in different ovarian cancer cell lines.MethodsThree different ovarian cancer cell lines (OVCAR-3, TOV-21G, and TOV-112D) were treated with chemotherapeutic drugs, alone or in combination with VPA. Cell viability (XTT assay), caspase-3 activity, and the expression of cell cycle– and apoptosis-related genes and proteins were assessed. Furthermore, the effects of these drugs on α-tubulin acetylation and DNA fragmentation were investigated.ResultsPaclitaxel and DOX decreased cell viability and increased caspase-3 activity, and co-treatment with VPA enhanced this effect. Carboplatin and CP had no effect. Responses to treatment with PAX and DOX together with VPA on gene expression profile were highly variable and depended on the cell line investigated. However, a common feature in all cell lines was an increased expression ofCDKN1A,CCNE1,PARP1, andPARP3. Co-treatment with VPA enhanced the effect of DOX and PAX on most protein expressions investigated in TOV-21G and TOV-112D cell lines, whereas in OVCAR-3, the most effect was seen with DOX with VPA. Valproic acid did not increase PTX-induced α-tubulin acetylation. An additive effect of DOX with VPA on DNA fragmentation was observed in TOV-21G and TOV-112D cell lines but not in the OVCAR-3.ConclusionsOur results indicate that VPA could be a promising agent in combined anticancer therapy for ovarian cancer, with the combination of VPA and DOX being the most effective. Certainly, additional in vivo and ex vivo experiments are necessary to investigate the molecular mechanisms of action underlying the cellular effects reported here and to study possible clinically relevant effects in ovarian cancer explants.

Download Full-text

ID: 45: EVALUATION OF CELLULAR MECHANISMS BY WHICH CINOBUFOTALIN INHIBITS OVARIAN CANCER CELL LINES FUNCTION

Journal of Investigative Medicine ◽

10.1136/jim-2016-000120.77 ◽

2016 ◽

Vol 64 (4) ◽

pp. 950.1-950 ◽

Cited By ~ 1

Author(s):

SH Afroze ◽

DC Zawieja ◽

R Tobin ◽

C Peddaboina ◽

MK Newell-Rogers ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Ovarian Cancer Cells ◽

Ovarian Cancer Cell Lines

ObjectiveCinobufotalin (CINO), a cardiotonic steroid (CTS) or bufadienolide, is extracted from the skin secretions of the traditional Chinese medicine giant toads (Chan su). CINO has been used as a cardiotonic, diuretic and a hemostatic agent. Previously we have shown that CINO inhibits the cytotrophoblast cell function. Recently other study has shown that CINO inhibits A549, a lung cancer cell function. In this study, we assessed the effect of CINO on three different ovarian cancer cell lines; SK-OV-3, CRL-1978 and CRL-11731 to confirm whether the effect of CINO is cell specific.Study DesignWe evaluated the effect of CINO on three ovarian cancer cells SK-OV-3, CRL-1978, and CRL-11731 function in vitro. Each Cell lines were treated with different concentrations of CINO (0.1, 1, 5 and 10 µM). For each cell line cell proliferation, migration and invasion were measured by using a CellTiter Assay (Promega), Cytoselect Assay (Cell Biolabs) and by using a FluoroBlock Assay (BD) respectively. Proliferating Cell Nuclear Antigen (PCNA) was also evaluated in cell lysates of CINO treated these 3 ovarian cancer cells by western blot analysis. Cell Cycle arrest and Cell viability were determined by fluorescence-activated cell sorting (FACS) analysis. We also performed Annexin V staining on CINO treated these 3 ovarian cancer cell lines by immunofluorescence to evaluate the pro-apoptotic protein expression. In addition mitochondrial membrane potential has also been measured for all these 3 ovarian cell lines after CINO treatment using MMP kit, by FACS analysis.ResultsConcentration of CINO at 0.5 µM inhibit SK-OV-3, CRL-1978, and CRL-11731 ovarian cancer cells proliferation, migration and invasion without cell death and loss of cell viability but cell viability differs for each cell line. Each cell lines differ in response to CINO doses for PCNA expression as well as Annexin V pro-apoptotic protein expression. CINO decreases mitochondrial membrane potential for SK-OV-3 but for CRL-1978 and CRL-11731 increases in response to CINO treatment.ConclusionCINO is cell specific, as each cancer cell line responds differently. These data demonstrate that the mode of action of CINO is different on these 3 types of ovarian cancer cells.

Download Full-text

Matrine inhibits ovarian cancer cell viability and promotes apoptosis by regulating the ERK/JNK signaling pathway via p38MAPK

Oncology Reports ◽

10.3892/or.2021.8033 ◽

2021 ◽

Vol 45 (5) ◽

Author(s):

Xin Liang ◽

Jianxin Ju

Keyword(s):

Ovarian Cancer ◽

Cell Viability ◽

Signaling Pathway ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Jnk Signaling ◽

Jnk Signaling Pathway

Download Full-text

Vitexin attenuates epithelial ovarian cancer cell viability and motility in vitro and carcinogenesis in vivo via p38 and ERK1/2 pathways related VEGFA

Annals of Translational Medicine ◽

10.21037/atm-20-5586 ◽

2020 ◽

Vol 8 (18) ◽

pp. 1139-1139

Author(s):

Shuzhen Zhao ◽

Xinlei Guan ◽

Ruijie Hou ◽

Xueying Zhang ◽

Fang Guo ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Viability ◽

Epithelial Ovarian Cancer ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Epithelial Ovarian Cancer Cell

Download Full-text

Combination of AKT inhibition with autophagy blockade effectively reduces ascites-derived ovarian cancer cell viability

Carcinogenesis ◽

10.1093/carcin/bgu049 ◽

2014 ◽

Vol 35 (9) ◽

pp. 1951-1961 ◽

Cited By ~ 30

Author(s):

Rohann J.M. Correa ◽

Yudith Ramos Valdes ◽

Teresa M. Peart ◽

Elena N. Fazio ◽

Monique Bertrand ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Viability ◽

Cancer Cell ◽

Ovarian Cancer Cell

Download Full-text

Sevoflurane but not propofol enhances ovarian cancer cell malignancy through regulating cellular metabolic and signalling mechanisms

10.22541/au.161425406.62861504/v1 ◽

2021 ◽

Author(s):

Cong Hu ◽

Bincheng Wang ◽

Zhigang Liu ◽

Qiling Chen ◽

Masashi Ishikawa ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cell Counting ◽

Immunofluorescent Staining ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Cellular Signalling

Background and Purpose: Surgery remains the first-line treatment of ovarian cancer. However, perioperative risk factors including the choice of anaesthetics may influence its recurrence after surgery. In the current study, it was hypothesised that inhalational anaesthetic sevoflurane and intravenous anaesthetic propofol might affect cancer cellular metabolism and signalling, which might interfere the malignancy of ovarian cancer cells. Experimental Approach: Cultured ovarian cancer cells were exposed to 2.5% sevoflurane or administered with 4 μg/mL propofol for 2 hours followed by 24 hours recovery. Their cell viability, proliferation, migration and invasion were assessed using cell counting kit-8, Ki-67 staining, wound healing and Transwell assay. Cellular signalling biomarkers were measured using immunofluorescent staining and/or Western blot. Cultured media were collected for 1H-NMR spectroscopy-based metabolomics analysis. Key Results: The cell viability, proliferation, migration, and invasion of ovarian cancer cells were enhanced by sevoflurane but suppressed by propofol. Sevoflurane increased the GLUT1, MPC1, GLUD1, p-Erk1/2, and HIF-1α expressions but decreased the PEDF expression. In contrast to the sevoflurane treatment, the “mirror changes” of these cellular markers were observed with propofol. Sevoflurane increased levels of isopropanol but decreased glucose and glutamine levels in the media, but the opposite changes of those metabolites were found after propofol treatment. Conclusion and Implications: These data indicated that unlike propofol, sevoflurane enhanced ovarian cancer cell metabolism and activated PEDF/Erk/HIF-1α cellular signalling pathway, suggesting that sevoflurane might have pro-tumour property but propofol might afford an anti-tumour property. The translational value of this work warrants further study.

Download Full-text

Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer Treatment

Diagnostics ◽

10.3390/diagnostics11030395 ◽

2021 ◽

Vol 11 (3) ◽

pp. 395

Author(s):

Anthony McDowell ◽

Kristen S. Hill ◽

J. Robert McCorkle ◽

Justin Gorski ◽

Yilin Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Dna Damage ◽

Cell Viability ◽

Cancer Treatment ◽

Cancer Cell ◽

Cell Cycle Progression ◽

Ovarian Cancer Cell ◽

G1 Arrest ◽

Cycle Progression

Background: Ovarian cancer is the deadliest gynecologic malignancy despite current first-line treatment with a platinum and taxane doublet. Artesunate has broad antineoplastic properties but has not been investigated in combination with carboplatin and paclitaxel for ovarian cancer treatment. Methods: Standard cell culture technique with commercially available ovarian cancer cell lines were utilized in cell viability, DNA damage, and cell cycle progression assays to qualify and quantify artesunate treatment effects. Additionally, the sequence of administering artesunate in combination with paclitaxel and carboplatin was determined. The activity of artesunate was also assessed in 3D organoid models of primary ovarian cancer and RNAseq analysis was utilized to identify genes and the associated genetic pathways that were differentially regulated in artesunate resistant organoid models compared to organoids that were sensitive to artesunate. Results: Artesunate treatment reduces cell viability in 2D and 3D ovarian cancer cell models. Clinically relevant concentrations of artesunate induce G1 arrest, but do not induce DNA damage. Pathways related to cell cycle progression, specifically G1/S transition, are upregulated in ovarian organoid models that are innately more resistant to artesunate compared to more sensitive models. Depending on the sequence of administration, the addition of artesunate to carboplatin and paclitaxel improves their effectiveness. Conclusions: Artesunate has preclinical activity in ovarian cancer that merits further investigation to treat ovarian cancer.

Download Full-text