scholarly journals Glutamine promotes ovarian cancer cell proliferation through the mTOR/S6 pathway

2015 ◽  
Vol 22 (4) ◽  
pp. 577-591 ◽  
Author(s):  
Lingqin Yuan ◽  
Xiugui Sheng ◽  
Adam K Willson ◽  
Dario R Roque ◽  
Jessica E Stine ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Stress Proteins ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Glutamine Metabolism ◽  
Dependent Manner ◽  
Ovarian Cancer Cell Lines

Glutamine is one of the main nutrients used by tumor cells for biosynthesis. Therefore, targeted inhibition of glutamine metabolism may have anti-tumorigenic implications. In the present study, we aimed to evaluate the effects of glutamine on ovarian cancer cell growth. Three ovarian cancer cell lines, HEY, SKOV3, and IGROV-1, were assayed for glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis, cell stress, and glucose/glutamine metabolism. Our results revealed that administration of glutamine increased cell proliferation in all three ovarian cancer cell lines in a dose dependent manner. Depletion of glutamine induced reactive oxygen species and expression of endoplasmic reticulum stress proteins. In addition, glutamine increased the activity of glutaminase (GLS) and glutamate dehydrogenase (GDH) by modulating the mTOR/S6 and MAPK pathways. Inhibition of mTOR activity by rapamycin or blocking S6 expression by siRNA inhibited GDH and GLS activity, leading to a decrease in glutamine-induced cell proliferation. These studies suggest that targeting glutamine metabolism may be a promising therapeutic strategy in the treatment of ovarian cancer.

Cell proliferation of human ovarian cancer is regulated by the opioid growth factor-opioid growth factor receptor axis

2009 ◽  
Vol 296 (6) ◽  
pp. R1716-R1725 ◽  
Author(s):  
Renee N. Donahue ◽  
Patricia J. McLaughlin ◽  
Ian S. Zagon
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Ovarian Cancer ◽  
Opioid Growth Factor ◽  
Ovarian Cancer Cell Lines

Ovarian cancer is the leading cause of death from gynecological malignancies. Understanding the biology of these tumors, as well as treatment modalities, has been challenging. The opioid growth factor (OGF; [Met5]-enkephalin) and the OGF receptor (OGFr) form an endogenous growth-regulating pathway in homeostasis and neoplasia. In this investigation, we examined the relationship of the OGF-OGFr axis to ovarian cancer, and defined its presence, function, and mechanisms. Using OVCAR-3 and SKOV-3 ovarian cancer cell lines, we found that OGF and OGFr were present and functional. Exogenous OGF was observed to have a dose-dependent, serum-independent, reversible, and receptor-mediated inhibitory action on cell proliferation that was dependent on RNA and protein synthesis. The repressive effect of OGF on cell proliferation also was observed in SW626, CAOV-3, and HEY ovarian cancer cell lines. Endogenous OGF was found to be constitutively produced and tonically active on cell replicative activities, with neutralization of this peptide accelerating cell proliferation. Silencing of OGFr using siRNA technology stimulated cell replication, documenting its integral role. The mechanism of OGF-OGFr action on DNA synthesis was related to the cyclin-dependent kinase inhibitory pathway because knockdown of p16 or p21 in OVCAR-3 cells, and p21 in SKOV-3 cells, eliminated OGF's inhibitory effect on growth. These data are the first to report that the OGF-OGFr system is a native biological regulator of cell proliferation in human ovarian cancer. This information will be important in designing treatment strategies for this deadly disease.

Implications of HER family inhibition in targeted therapy of ovarian cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13120-13120
Author(s):  
S. L. Bull ◽  
J. O. Schorge ◽  
M. J. Peyton ◽  
L. Xiang ◽  
D. S. Miller ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Growth Inhibition ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Her2 Expression ◽  
Her Family ◽  
Ovarian Cancer Cell Lines

13120 Background: The human epidermal receptor (HER) family couples binding of extracellular ligands to intracellular tyrosine kinase (TK) signal transduction pathways, contributing to cellular proliferation. Overexpression of HER family members has been associated with poor prognosis in ovarian cancer. There is growing evidence to support that none of the individual HER members can be considered as the stand-alone target in ovarian cancer and that cooperation between them influences therapeutic response. To evaluate this receptor cooperation in ovarian cancer our goal was to determine HER family expression and to quantify inhibition of HER1 alone compared to inhibition of HER1/HER2 combined. Methods: HER1, HER2, HER3 and HER4 expression was determined by Western blot in 9 ovarian cancer cell lines. Ovarian cancer cell proliferation was determined after inhibition of HER1 using the monoclonal antibody cetuximab, the TK inhibitor gefitinib, or combination of the two. To quantify the combined inhibition of HER1/HER2, 3 cell lines were selected with variable HER1 and HER2 expression. Cell proliferation was then determined in these 3 cell lines after treatment with cetuximab combined with the monoclonal HER2 antibody, trastuzumab. IC50 values were calculated for all treatment arms and compared. A lung cancer cell line (HCC827), with a HER1 TK mutation and sensitivity to gefitinib and cetuximab, was used as a positive control. Results: HER1 was overexpressed in 3/9 ovarian cancer cell lines, HER2 in 1/9, HER3 in 2/9, and HER4 in 4/9. Minimal to no growth inhibition was seen in the 9 cell lines after blocking HER1 with cetuximab, gefitinib, or the combination of both. In the 3 cell lines selected for HER1 and HER2 expression, there was no growth inhibition achieved despite combining cetuximab with trastuzumab. However, this treatment combination increased resistance in 1 of the 3 cell lines (HCC60), noted to overexpress HER1, 2, and 4. Conclusions: Ovarian cancer has variable HER family expression. No correlation was found between HER1 and HER2 overexpression and response to their targeted inhibition. Our findings support the concept the entire HER family plays a role in ovarian cancer growth and suggest an equilibrium shift of HER heterodimerization may play an important role in maintaining cell signaling. No significant financial relationships to disclose.

Jatropha-6(17),11E-diene class derivatives induce apoptosis effects in OVCAR-3 and Caov-4 ovarian cancer cell lines via a mitochondrial pathway

2017 ◽  
Vol 95 (6) ◽  
pp. 616-627 ◽  
Author(s):  
Behzad Bahmani ◽  
Mohammad Keyvanloo Shahrestanaki ◽  
Mustafa Ghanadian ◽  
Sima Hajiahmadi ◽  
Mahmoud Aghaei
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Caspase 3 ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ros Generation ◽  
Dependent Manner ◽  
Compound C ◽  
Ovarian Cancer Cell Lines

We investigated the molecular mechanism of apoptosis induced by novel jatropha-6(17),11E-diene class derivatives, compounds A, B, and C that were extracted from Euphorbia osyridea Boiss, in the ovarian cancer cell lines Caov-4 and OVCAR-3. The OVCAR-3 and Caov-4 cell lines were treated with different concentrations of these compounds. Cytotoxicity was evaluated using MTT, clonogenic survival assay, and flow cytometry assays. The production of reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and the activity of caspase 3 and 9 were evaluated. Compounds A, B, and C reduced cell viability in a dose-dependent manner (P < 0.05). The IC50 values were calculated as 46.27 ± 3.86, and 38.81 ± 3.30 μmol/L for compound A, 36.48 ± 3.18 and 42.59 ± 4.50 μmol/L for compound B, and 85.86 ± 6.75 and 75.65 ± 2.56 μmol/L for compound C against the Caov-4 and OVCAR-3 cell lines, respectively. Apoptosis evaluation showed that jatrophane derivatives increase both early and late apoptosis (P < 0.01). These compounds also increased ROS generation, ΔΨm, and the activity of caspase 3 and 9 in the treated cells. These results showed that compounds A and B have significant inhibitory effects on OVCAR-3 and Caov-4 proliferation and induction of apoptosis.

scholarly journals Anti-proliferative activities of Byrsocarpus coccineus using ovarian cancer cell lines

2020 ◽  
Author(s):  
Caroline Ukwade ◽  
Osaretin Ebuehi ◽  
Rashidat Adisa ◽  
Santos Singh ◽  
Rajesh Singh
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Leaf Extract ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Dependent Manner ◽  
Inhibition Of Proliferation ◽  
Ovarian Cancer Cell Lines

Abstract Background: Ovarian cancer is one of the most lethal tumors of gynecologic malignancies, due to lack of early detection, and a high rate of metastasis. The standard treatment is surgery and cytotoxic chemotherapy, but due to its cost and side effects, medicinal plants are widely used in developing countries. Byrsocarpus coccineus plant preparation, has been administered to patients traditionally in the management of tumour in Nigeria. In this study, we investigated the anti-proliferative effects of B. coccineus ethanol leaf extract against OVCAR3 and SW626 ovarian cancer cell lines. After treatment of the two cell lines with the extracts, analyses were carried out to determine inhibition of proliferation and expression of cell cycle markers, pro-apoptotic and anti-apoptotic markers. Results: Results showed that B. coccineus ethanol leaf extract, significantly inhibited cell migration and colony formation in OVCAR3 and SW626 treated cells in a dose-dependent manner. Results also show that B. coccineus ethanol leaf extract modulated the expression of p53 gene, cell cycle progression, anti-apoptotic and pro-apoptotic genes. Conclusions: These results suggest that B. coccineus have anti-proliferative properties and could induce apoptosis. Further investigation will be carried out to isolate bioactive compounds for the treatment of ovarian cancer.

scholarly journals Anticancer Activity of Gukulenin A Isolated from the Marine Sponge Phorbas gukhulensis In Vitro and In Vivo

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 126 ◽  
Author(s):  
Ji-Hye Ahn ◽  
Jeong-Hwa Woo ◽  
Jung-Rae Rho ◽  
Jung-Hye Choi
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cell Lines ◽  
Cancer Cell ◽  
Marine Sponge ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Dependent Manner ◽  
Ovarian Cancer Cell Lines ◽  
A2780 Cell

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.

Gedunin, a Novel Natural Substance, Inhibits Ovarian Cancer Cell Proliferation

2009 ◽  
Vol 19 (9) ◽  
pp. 1564-1569 ◽  
Author(s):  
Siddharth G. Kamath ◽  
Ning Chen ◽  
Yin Xiong ◽  
Robert Wenham ◽  
Sachin Apte ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Expression Data ◽  
Ovarian Cancer Cell Lines

The discovery of more active therapeutic compounds is essential if the outcome for patients with advanced-stage epithelial ovarian cancer is to be improved. Gedunin, an extract of the neem tree, has been used as a natural remedy for centuries in Asia. Recently, gedunin has been shown to have potential in vitro antineoplastic properties; however, its effect on ovarian cancer cells is unknown. We evaluated the in vitro effect of gedunin on SKOV3, OVCAR4, and OVCAR8 ovarian cancer cell lines proliferation, alone and in the presence of cisplatin. Furthermore, we analyzed in vitro gedunin sensitivity data, integrated with genome-wide expression data from 54 cancer cell lines in an effort to identify genes and molecular pathways that underlie the mechanism of gedunin action. In vitro treatment of ovarian cancer cell lines with gedunin alone produced up to an 80% decrease in cell proliferation (P < 0.01) and, combining gedunin with cisplatin, demonstrated up to a 47% (P < 0.01) decrease in cell proliferation compared with cisplatin treatment alone. Bioinformatic analysis of integrated gedunin sensitivity and gene expression data identified 52 genes to be associated with gedunin sensitivity. These genes are involved in molecular functions related to cell cycle control, carcinogenesis, lipid metabolism, and molecular transportation. We conclude that gedunin has in vitro activity against ovarian cancer cells and, further, may enhance the antiproliferative effect of cisplatin. The molecular determinants of in vitro gedunin response are complex and may include modulation of cell survival and apoptosis pathways.

scholarly journals E2F8 Induces Cell Proliferation and Invasion through the Epithelial–Mesenchymal Transition and Notch Signaling Pathways in Ovarian Cancer

2020 ◽  
Vol 21 (16) ◽  
pp. 5813
Author(s):  
Kyung Jin Eoh ◽  
Hee Jung Kim ◽  
Jong Woo Lee ◽  
Lee Kyung Kim ◽  
Sun-Ae Park ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Mesenchymal Transition ◽  
Ovarian Cancer Cell Lines

Background: Despite the recent research implicating E2F8 (E2F Transcription Factor 8) in cancer, the role of E2F8 in the progression of ovarian cancer has remained unclear. Hence, we explored the bio-functional effects of E2F8 knockdown on ovarian cancer cell lines in vitro and in vivo. Methods: The expression of E2F8 was compared between ovarian cancer and noncancer tissues, and its association with the progression-free survival of ovarian cancer patients was analyzed. To demonstrate the function of E2F8 in cell proliferation, migration, and invasion, we employed RNA interference to suppress E2F8 expression in ovarian cancer cell lines. Finally, the effect of E2F8 knockdown was investigated in a xenograft mouse model of ovarian cancer. Results: Ovarian cancer tissue exhibited significantly higher E2F8 expression compared to that of normal ovarian tissue. Clinical data showed that E2F8 was a significant predictor of progression-free survival. Moreover, the prognosis of the ovarian cancer patients with high E2F8 expression was poorer than that of the patients with low E2F8 expression. In vitro experiments using E2F8-knockdown ovarian cancer cell lines demonstrated that E2F8 knockdown inhibited cell proliferation, migration, and tumor invasion. Additionally, E2F8 was a potent inducer and modulator of the expression of epithelial–mesenchymal transition and Notch signaling pathway-related markers. We confirmed the function of E2F8 in vivo, signifying that E2F8 knockdown was significantly correlated with reduced tumor size and weight. Conclusions: Our findings indicate that E2F8 is highly correlated with ovarian cancer progression. Hence, E2F8 can be utilized as a prognostic marker and therapeutic target against ovarian malignancy.

scholarly journals Niosome-encapsulated balanocarpol: compound isolation, characterisation, and cytotoxicity evaluation against human breast and ovarian cancer cell lines

2020 ◽  
Vol 31 (19) ◽  
pp. 195101 ◽  
Author(s):  
Mohammad A Obeid ◽  
Siti Aisya S Gany ◽  
Alexander I Gray ◽  
Louise Young ◽  
John O Igoli ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Breast ◽  
Breast And Ovarian Cancer ◽  
Ovarian Cancer Cell Lines
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