Role of notch pathway and HNF1 in cell death induced by HDACs inhibitors in ovarian cancer cell lines, serous and clear cells

Gukulenin A is a bis-tropolone tetraterpenoid isolated from the marine sponge Phorbas gukhulensis. In this study, we examined the anticancer activities of gukulenin A in ovarian cancer cell lines (A2780, SKOV3, OVCAR-3, and TOV-21G) and in an ovarian cancer mouse model generated by injecting A2780 cells. We found that gukulenin A suppressed tumor growth in A2780-bearing mice. Gukulenin A markedly inhibited cell viability in four ovarian cancer cell lines, including the A2780 cell line. Gukulenin A treatment increased the fraction of cells accumulated at the sub G1 phase in a dose-dependent manner and the population of annexin V-positive cells, suggesting that gukulenin A induces apoptotic cell death in ovarian cancer cells. In addition, gukulenin A triggered the activation of caspase-3, -8, and -9, and caspase inhibitors attenuated gukulenin A-induced A2780 cell death. The results suggest that gukulenin A may be a potential therapeutic agent for ovarian cancer.

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PTPRK Expression Is Downregulated in Drug Resistant Ovarian Cancer Cell Lines, and Especially in ALDH1A1 Positive CSCs-Like Populations

International Journal of Molecular Sciences ◽

10.3390/ijms20082053 ◽

2019 ◽

Vol 20 (8) ◽

pp. 2053 ◽

Cited By ~ 3

Author(s):

Świerczewska ◽

Sterzyńska ◽

Wojtowicz ◽

Kaźmierczak ◽

Iżycki ◽

...

Keyword(s):

Ovarian Cancer ◽

Drug Resistance ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Acquired Resistance ◽

Cancer Cell Lines ◽

Pcr Analysis ◽

Ovarian Cancer Cell Lines

Background: Ovarian cancer is the 7th most common cancer and 8th most mortal canceramong woman. The standard treatment includes cytoreduction surgery followed bychemotherapy. Unfortunately, in most cases, after treatment, cancer develops drug resistance.Decreased expression and/or activity of protein phosphatases leads to increased signaltransduction and development of drug resistance in cancer cells. Methods: Using sensitive (W1,A2780) and resistant ovarian cancer cell lines, the expression of Protein Tyrosine PhosphataseReceptor Type K (PTPRK) was performed at the mRNA (real‐time PCR analysis) and protein level(Western blot, immunofluorescence analysis). The protein expression in ovarian cancer tissues wasdetermined by immunohistochemistry. Results: The results showed a decreased level of PTPRKexpression in ovarian cancer cell lines resistant to cisplatin (CIS), paclitaxel (PAC), doxorubicin(DOX), topotecan (TOP), vincristine (VIN) and methotrexate (MTX). Additionally, the lowerPTPRK expression was observed in Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1)positive cancer stem cells (CSCs) population, suggesting the role of PTPRK downregulation inprimary as well as acquired resistance to cytotoxic drugs. Conclusions: These results provideimportant insights into the role of PTPRK in mechanism leading to drug resistance in ovariancancer and has raised important questions about the role of imbalance in processes ofphosphorylation and dephosphorylation.

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Functional redundancy of the Notch pathway in ovarian cancer cell lines

Oncology Letters ◽

10.3892/ol.2016.4959 ◽

2016 ◽

Vol 12 (4) ◽

pp. 2686-2691 ◽

Cited By ~ 1

Author(s):

Fernanda Silva ◽

Ana Félix ◽

Jacinta Serpa

Keyword(s):

Ovarian Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Notch Pathway ◽

Cancer Cell Lines ◽

Functional Redundancy ◽

Ovarian Cancer Cell Lines

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Role of Differential Expression of miRNAs miR-125a, miR-200a and miR-199a in Metastatic Property of Ovarian Cancer Cell lines and Relationship between miR-199a and its Predicted Target Protein GSK3β

10.1101/2020.04.11.037424 ◽

2020 ◽

Author(s):

Divya RSJB Rana ◽

Lin Xu ◽

Jie Zhang

Keyword(s):

Ovarian Cancer ◽

Differential Expression ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Glycogen Synthase ◽

Gynecological Cancer ◽

Cancer Cell Lines ◽

Ovarian Cancer Cell Lines

AbstractOvarian cancer is a gynecological cancer of high mortality rate. Most of the ovarian cancer origin from the surface epithelium of the ovaries. Ovarian cancers gain metastatic and invasive properties from various biochemical events taking place during tumorogenesis. MicroRNAs (miRNA) are non-coding RNAs and they have an important function of inhibiting translation of specific mRNAs in the cytoplasm. Present study uses two ovarian cancer cell lines as model to study the differential expression of miR-125a, miR-200a, and miR-199a, and provides indirect proof for possible relationship between miR-199a and its predicted target gene Glycogen Synthase Kinase 3 β (GSK3β). As expected the expression of these three microRNAs are decreased in metastatic ovarian cancer cell line A2780 compared to epithelial ovarian cancer OVCAR3. Reciprocal expression pattern of miR-199a and its predicted target GSK3β was found in two different cell lines providing information on possible inhibitory role of miR-199a against GSK3β.

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The significance of HERC5, IFIH1, SAMD4, SEMA3A and MCTP1 genes expression in resistance to cytotoxic drugs in ovarian cancer cell lines

Medical Journal of Cell Biology ◽

10.2478/acb-2021-0019 ◽

2021 ◽

Vol 9 (3) ◽

pp. 138-147

Author(s):

Marta Nowacka ◽

Barbara Ginter-Matuszewska ◽

Monika Świerczewska ◽

Michał Nowicki ◽

Maciej Zabel ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Quantitative Polymerase Chain Reaction ◽

Cancer Cell Lines ◽

Resistance Development ◽

Ovarian Cancer Cell Lines ◽

Genes Expression

Abstract Resistance to chemotherapy is the main obstacle in contemporary ovarian cancer treatment. The aim of this study was the evaluation of expression of HERC5, IFIH1, SAMD4, MCTP1 and SEMA3A mRNA and assessment their role in resistance to cisplatin, paclitaxel, doxorubicin and topotecan in seven ovarian cancer cell lines. MTT assay was used in resistance assessment. Quantitative polymerase chain reaction was performed to measure the expression levels of the genes. We observed different levels of resistance among cell lines. The resistance was not related to the expression of drug transporters genes. The expression of HERC5 and IFIH1 genes was upregulated, and the expression of SEMA3A gene was downregulated. Expression of SAMD4 was upregulated in PEA1, PEA2, and PEO23 cell lines, and expression of MCTP1 was downregulated in A2780, PEA2, and PEO23 cell lines. Upregulation of HERC5, IFIH1, and SAMD4 and downregulation of SEMA3A and MCTP1 in TOP-resistant ovarian cancer cell lines may suggest some role of those genes in topotecan resistance development.

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Bexarotene-induced Cell Death in Ovarian Cancer Cells Through Caspase-4–mediated pyroptosis

10.21203/rs.3.rs-1026249/v1 ◽

2021 ◽

Author(s):

Tatsuya Kobayashi ◽

Akira Mitsuhashi ◽

Piao Hongying ◽

Masashi Shioya ◽

Kyoko Nishikimi ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Death ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Ovarian Cancer Cells ◽

Mrna Levels ◽

Ovarian Cancer Cell Lines

Abstract Purpose: Bexarotene is selectively activates retinoid X recepto, whichr is a commonly used anticancer agent for cutaneous T-cell lymphoma. In this study, we aimed to investigate the anticancer effect of bexarotene and its underlying mechanism in ovarian cancer in vitro.Methods: The ES2 and NIH:OVACAR3 ovarian cancer cell lines were treated with 0, 5, 10, or 20 µM bexarotene. After 24 hours, cell number measurement and lactate dehydrogenase (LDH) cytotoxicity assay were performed. The effect of bexarotene on CDKN1A expression, pyroptosis, and apoptosis were evaluated.Results: Bexarotene reduced cell proliferation in all concentrations in both cells. At concentrations above 10 µM, it increased extracellular LDH activity with cell rupture. In both cells, 10 µM bexarotene treatment increased the CDKN1A mRNA levels and reduced cell cycle related protein expression. In ES2 cells, caspase-4 and GSDME were activated, whereas caspase-3 was not, indicating that bexarotene-induced cell death might be pyroptosis. Conclusion: A clinical setting dose of bexarotene induced cell cycle arrest and cell death through caspase-4–mediated pyroptosis in ovarian cancer cell lines. Thus, bexarotene may serve as a novel therapeutic agent for ovarian cancer.

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Family With Sequence Similarity 46 Member A Confers Chemo-Resistance to Ovarian Carcinoma via TGF-β/Smad2 Signaling

10.21203/rs.3.rs-951414/v1 ◽

2021 ◽

Author(s):

Suiying Liang ◽

Yueyang Liu ◽

Jianhui He ◽

Tian Gao ◽

Lanying Li ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Progression ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Ovarian Cancer Cells ◽

Ovarian Cancer Cell Lines

Abstract Purpose: Ovarian cancer is the most lethal malignancy with depressive 5-year survival rate, mainly due to patients with advanced stages experience tumor recurrence and resistance to the current chemotherapeutic agents. Thus, discovering the underlying molecular mechanisms involved in chemo-resistance is crucial for management of treatment to improve therapeutic outcomes. Methods: The protein and mRNA expression of FAM46A in ovarian cancer cell lines and patient tissues were determined using Real-time PCR and Western blot and IHC respectively. Functional assays, such as MTT, FACS assay used to determine the oncogenic role of FAM46A in human ovarian cancer progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of FAM46A promotes chemoresistance in ovarian cancer cells. Results: In the current study, we found overexpression of FAM46A expression in ovarian cancer patients demonstrated an aggressive phenotype and poor prognosis. Furthermore, FAM46A overexpression in ovarian cancer cells demonstrated higher CDDP resistance ability; however, inhibition of FAM46A sensitized ovarian cancer cell lines to CDDP cytotoxicity both in vitro and in vivo. Mechanically, upregulation of FAM46A activated transforming growth factor-β (TGF-β)/Smad signaling and upregulated the levels of nuclear Smad2. Conclusions: Taken together, our results highlight the important oncogenic role of FAM46A in ovarian cancer progression and might provide a potential clinical target for patients with chemoresistant ovarian cancer.

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