scholarly journals Theasaponin E1 Inhibits Platinum-Resistant Ovarian Cancer Cells through Activating Apoptosis and Suppressing Angiogenesis

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1681
Author(s):  
Bo Li ◽  
Tuantuan Tong ◽  
Ning Ren ◽  
Gary O. Rankin ◽  
Yon Rojanasakul ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Protein Expression ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Akt Signaling ◽  
Ovarian Cancer Cells ◽  
Potential Candidate ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy

Novel therapeutic strategies for ovarian cancer treatment are in critical need due to the chemoresistance and adverse side effects of platinum-based chemotherapy. Theasaponin E1 (TSE1) is an oleanane-type saponin from Camellia sinensis seeds. Its apoptosis-inducing, cell cycle arresting and antiangiogenesis activities against platinum-resistant ovarian cancer cells were elucidated in vitro and using the chicken chorioallantoic membrane (CAM) assay. The results showed that TSE1 had more potent cell growth inhibitory effects on ovarian cancer OVCAR-3 and A2780/CP70 cells than cisplatin and was lower in cytotoxicity to normal ovarian IOSE-364 cells. TSE1 significantly induced OVCAR-3 cell apoptosis via the intrinsic and extrinsic apoptotic pathways, slightly arresting cell cycle at the G2/M phase, and obviously inhibited OVCAR-3 cell migration and angiogenesis with reducing the protein secretion and expression of vascular endothelial growth factor (VEGF). Western bolt assay showed that Serine/threonine Kinase (Akt) signaling related proteins including Ataxia telangiectasia mutated kinase (ATM), Phosphatase and tensin homolog (PTEN), Akt, Mammalian target of rapamycin (mTOR), Ribosome S6 protein kinase (p70S6K) and e IF4E-binding protein 1(4E-BP1) were regulated, and Hypoxia inducible factor-1α (HIF-1α) protein expression was decreased by TSE1 in OVCAR-3 cells. Moreover, TSE1 treatment potently downregulated protein expression of the Notch ligands including Delta-like protein 4 (Dll4) and Jagged1, and reduced the protein level of the intracellular domain (NICD) of Notch1. Combination treatment of TSE1 with the Notch1 signaling inhibitor tert-butyl (2S)-2-[[(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoyl]amino]-2-phenylacetate (DAPT), or the Akt signaling inhibitor wortmannin, showed a stronger inhibition toward HIF-1α activation compared with single compound treatment. Taken together, TSE1 might be a potential candidate compound for improving platinum-resistant ovarian cancer treatment via Dll4/Jagged1-Notch1-Akt-HIF-1α axis.

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.

MicroRNA-301a Promotes Cell Proliferation and Resistance to Apoptosis through PTEN/PI3K/Akt Signaling Pathway in Human Ovarian Cancer

2021 ◽  
pp. 1-9
Author(s):  
Jie Ni ◽  
Ying Chen ◽  
Beibei Fei ◽  
Yan Zhu ◽  
Yibei Du ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Critical Role ◽  
Akt Signaling ◽  
Ovarian Cancer Cells ◽  
Control Group ◽  
Akt Signaling Pathway

Background: MicroRNAs are endogenous small noncoding RNAs, which play a critical role in regulating various biological and pathologic processes. Furthermore, miR-301a has been detected to be overly expressed in tumorigenic progression of ovarian cancer. However, the effects of miR-301a on ovarian cancer are still unclear. Objective: The objective of this study is to investigate the molecular mechanisms of miR-301a in epithelial ovarian cancer cells. Methods: The miR-301a expression in ovarian cancer cells was detected. Then, cell proliferation, cell cycle, and apoptosis of the miR-301a-mimic-transfected ovarian cancer cells were determined, as well as the effects of the miR-301a mimic on the PTEN/phosphoinositide 3-kinase (PI3K) signaling pathway were explored. Results: We found that the miR-301a expression levels were markedly upregulated in ovarian cancer tissues and cells, and upregulation of miR-301a-promoted cell viability and proliferation. Our results also showed that the miR-301a-mimic accelerated cell cycle progression of ovarian cancer cells by targeting the CDK4/Cyclin-D1 pathway but not the CDK2/Cyclin-E pathway. Moreover, transfection of the miR-301a mimic into ovarian cancer cells could decrease the PTEN expression while increasing the PI3K and Akt phosphorylation, as compared with the miR-301a inhibitor group and the negative control group. Conclusion: Therefore, miR-301a should be an oncogene in ovarian cancer, and overexpression of miR-301a promoted proliferation of ovarian cancer cells by modulating the PTEN/PI3K/Akt signaling pathway.

Lupeol Inhibits Proliferation and Promotes Apoptosis of Ovarian Cancer Cells by Inactivating Phosphoinositide-3-Kinase/Protein Kinase B/ Mammalian Target of Rapamycin Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 206-210
Author(s):  
Feng Chen ◽  
Bei Zhang
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Protein Kinase ◽  
Cell Viability ◽  
Cancer Cells ◽  
Protein Kinase B ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Ovarian Cancer Cells ◽  
Phosphoinositide 3 Kinase

Lupeol exhibits multiple pharmacological activities including, anticancerous, anti-inflammatory, and antioxidant. The aim of this study was to explore the anticancerous activity of lupeol on ovarian cancer cells and examine its mechanism of action. To this end, increasing concentrations of lupeol on cell viability, cell cycle, and apoptosis in Caov-3 cells were evaluated. Lupeol inhibited cell viability, induced G1 phase arrest in cell cycle, increased cell apoptosis, and inhibited the ratio of phospho-Akt/protein kinase B and phospho-mammalian target of rapamycin/mammalian target of rapamycin. In conclusion, these data suggest that lupeol may play a therapeutic role in ovarian cancer.

Adenosine Analogues as Opposite Modulators of the Cisplatin Resistance of Ovarian Cancer Cells

2019 ◽  
Vol 19 (4) ◽  
pp. 473-486 ◽  
Author(s):  
Katarzyna Bednarska-Szczepaniak ◽  
Damian Krzyżanowski ◽  
Magdalena Klink ◽  
Marek Nowak
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Biology ◽  
Immune Cell ◽  
Immunosuppressive Agents ◽  
Cell Activity ◽  
Ovarian Cancer Cells ◽  
Adenosine Analogues

Background: Adenosine released by cancer cells in high amounts in the tumour microenvironment is one of the main immunosuppressive agents responsible for the escape of cancer cells from immunological control. Blocking adenosine receptors with adenosine analogues and restoring immune cell activity is one of the methods considered to increase the effectiveness of anticancer therapy. However, their direct effects on cancer cell biology remain unclear. Here, we determined the effect of adenosine analogues on the response of cisplatinsensitive and cisplatin-resistant ovarian cancer cells to cisplatin treatment. Methods: The effects of PSB 36, DPCPX, SCH58261, ZM 241385, PSB603 and PSB 36 on cisplatin cytotoxicity were determined against A2780 and A2780cis cell lines. Quantification of the synergism/ antagonism of the compounds cytotoxicity was performed and their effects on the cell cycle, apoptosis/necrosis events and cisplatin incorporation in cancer cells were determined. Results: PSB 36, an A1 receptor antagonist, sensitized cisplatin-resistant ovarian cancer cells to cisplatin from low to high micromolar concentrations. In contrast to PSB 36, the A2AR antagonist ZM 241385 had the opposite effect and reduced the influence of cisplatin on cancer cells, increasing their resistance to cisplatin cytotoxicity, decreasing cisplatin uptake, inhibiting cisplatin-induced cell cycle arrest, and partly restoring mitochondrial and plasma membrane potentials that were disturbed by cisplatin. Conclusion: Adenosine analogues can modulate considerable sensitivity to cisplatin of ovarian cancer cells resistant to cisplatin. The possible direct beneficial or adverse effects of adenosine analogues on cancer cell biology should be considered in the context of supportive chemotherapy for ovarian cancer.

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.

CNOT7 modulates biological functions of ovarian cancer cells via AKT signaling pathway

Life Sciences ◽  
2021 ◽  
Vol 268 ◽  
pp. 118996
Author(s):  
Jiangtao Yu ◽  
Xiaoli Hu ◽  
Xiuxiu Chen ◽  
Qiangyong Zhou ◽  
Qi Jiang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Ovarian Cancer Cells ◽  
Biological Functions ◽  
Akt Signaling Pathway
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