scholarly journals Induced growth of BG-1 ovarian cancer cells by 17β-estradiol or various endocrine disrupting chemicals was reversed by resveratrol via downregulation of cell cycle progression

2012 ◽  
Author(s):  
Kyung-Chul Choi
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Endocrine Disrupting Chemicals ◽  
Ovarian Cancer Cells ◽  
Cycle Progression ◽  
Endocrine Disrupting ◽  
17Β Estradiol

Evaluation of GPER agonist G-1 combined with navitoclax in platinum-resistant and -sensitive ovarian cancer cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13563-e13563
Author(s):  
Dennis C. DeSimone ◽  
Trung T. Nguyen ◽  
Eugen Brailiou ◽  
John C. Taylor ◽  
Gabriela Cristina Brailoiu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Parp Cleavage ◽  
Ovarian Cancer Cells ◽  
Cycle Progression ◽  
Platinum Based Chemotherapy ◽  
Induced Apoptosis ◽  
In Cells

e13563 Background: Most ovarian cancer patients are treated with platinum-based chemotherapy but eventually relapse with incurable disease. The G protein-coupled estrogen receptor GPER (GPR30) mediates Ca2+ mobilization in response to estrogen and G-1, a synthetic agonist. Large and sustained Ca2+ responses can lead to mitochondrial Ca2+ overload and apoptosis. Hence, we evaluated whether G-1 could induce apoptosis in cisplatin-sensitive A2780 and isogenic cisplatin–resistant CP70 (14-fold resistant), C30 (70-fold resistant) and C200 (157-fold resistant) human ovarian cancer cells. Bcl-2 and Bcl-xL protect mitochondria from Ca2+overload, and were overexpressed in these cisplatin-resistant cells; thus we also examined combining the Bcl-2 family inhibitor navitoclax with G-1. Methods: Cytoplasmic [Ca2+]c and mitochondrial [Ca2+]m were monitored using microscopy and fluorescent Ca2+ probes. Cell cycle, apoptosis and mitochondrial membrane potential (MMP) were assessed by flow cytometry of propidium iodide, Annexin V and DiIC1(5) -stained cells. The intracellular Ca2+ chelator BAPTA was used to block Ca2+mobilization. Results: Expression of the 53kDa GPER but not the 38 kDa isoform progressively increased with increasing cisplatin resistance. G-1 elicited sustained [Ca2+]c rises that correlated with 53 kDa GPER expression, followed by rises in [Ca2+]m. In all cells, 2.5 μM G-1 blocked cell cycle progression at G2/M, inhibited proliferation, and induced apoptosis (A2780 > C30 > CP70 ≥ C200). G-1 induced p53, caspase-3 and PARP cleavage, and MMP loss. BAPTA prevented G-1’s cell cycle and apoptotic effects in cells showing large Ca2+ mobilization responses but did not in cells with small Ca2+responses. Combining navitoclax with G-1 superadditively decreased cell viability and increased apoptosis. Conclusions: G-1 blocked cell cycle progression and induced apoptosis via a Ca2+-dependent pathway in cells expressing high 53 kDa GPER levels, but via a Ca2+-independent pathway in cells with low 53 kDa GPER expression. G-1 also interacted cooperatively with naviticlax. Therefore, G-1 plus navitoclax shows potential for therapeutic use in platinum-sensitive and -resistant ovarian cancer.

scholarly journals A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities

2016 ◽  
Vol 39 (3) ◽  
pp. 871-888 ◽  
Author(s):  
Youlin Deng ◽  
Zhongliang Wang ◽  
Fugui Zhang ◽  
Min Qiao ◽  
Zhengjian Yan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Anticancer Activities ◽  
Cycle Progression ◽  
Igf Signaling

Background/Aims: Ovarian cancer is the most lethal gynecologic malignancy, and there is an unmet clinical need to develop new therapies. Although showing promising anticancer activity, Niclosamide may not be used as a monotherapy. We seek to investigate whether inhibiting IGF signaling potentiates Niclosamide's anticancer efficacy in human ovarian cancer cells. Methods: Cell proliferation and migration are assessed. Cell cycle progression and apoptosis are analyzed by flow cytometry. Inhibition of IGF signaling is accomplished by adenovirus-mediated expression of siRNAs targeting IGF-1R. Cancer-associated pathways are assessed using pathway-specific reporters. Subcutaneous xenograft model is used to determine anticancer activity. Results: We find that Niclosamide is highly effective on inhibiting cell proliferation, cell migration, and cell cycle progression, and inducing apoptosis in human ovarian cancer cells, possibly by targeting multiple signaling pathways involved in ELK1/SRF, AP-1, MYC/MAX and NFkB. Silencing IGF-1R exert a similar but weaker effect than that of Niclosamide's. However, silencing IGF-1R significantly sensitizes ovarian cancer cells to Niclosamide-induced anti-proliferative and anticancer activities both in vitro and in vivo. Conclusion: Niclosamide as a repurposed anticancer agent may be more efficacious when combined with agents that target other signaling pathways such as IGF signaling in the treatment of human cancers including ovarian cancer.

STAT3 Inhibitor Napabucasin Inhibits Tumor Growth and Cooperates with Proteasome Inhibition in Human Ovarian Cancer Cells

2021 ◽  
Vol 16 ◽  
Author(s):  
Yao Liu ◽  
Xiaolin Peng ◽  
Hui Li ◽  
Wenhui Jiao ◽  
Xin Peng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Single Agent ◽  
Treatment Strategies ◽  
Ovarian Cancer Cells ◽  
Autophagic Flux ◽  
Antitumor Effects ◽  
Proliferative Effect

Background: Ovarian cancer is a disease with the highest mortality in gynecologic malignancies. Activation of STAT3 pathway is well known to be associated with tumor progression and metastasis in a number of cancers including ovarian cancer. Therefore, STAT3 may be an ideal target for ovarian cancer treatment. Objective: The present study aims to determine the antitumor activity of STAT3 inhibitor Napabucasin as a single agent or in combination with proteasome inhibitor MG-132 in ovarian cancer cells. Methods: MTT was performed to determine the anti-proliferative effect of Napabucasin on ovarian cancer SKOV-3 cells. The involved anti-tumor mechanism was explored by flow cytometry, qRT-PCR and western blot. MDC staining and tandem mRFP-GFP-LC3 fluorescence microscopy were used to analyze the autophagy inducing capability of Napabucasin with or without MG-132. The combinational anticancer effect of Napabucasin and MG-132 was evaluated according to Chou and Talalay’s method (1984). Results: Napabucasin showed obvious tumor-inhibitory effects against SKOV-3 cells. Treatment by Napabucasin arrested cell cycle progression in G2/M phase. Mechanistically, elevated expression of p21 may contribute to the blockade of cell cycle. Moreover, we demonstrated that Napabucasin induced autophagy in SKOV-3 cells by using various assays including MDC staining, autophagic flux examination, and detection of the autophagy markers. In addition, combination of Napabucaisin with MG-132 exhibited significant synergistic anti-proliferative effect, probably by inducing apoptosis through a mitochondria-dependent pathway. The two compounds induced pro-survival autophagies, and co-treated with autophagy inhibiter might further enhance their antitumor effects. Conclusion: Napabucasin alone or in combination with MG-132 might be promising treatment strategies for ovarian cancer patients.

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