scholarly journals A novel small molecule LLL12B inhibits STAT3 signaling and sensitizes ovarian cancer cell to paclitaxel and cisplatin

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0240145
Author(s):  
Ruijie Zhang ◽  
Xiaozhi Yang ◽  
Dana M. Roque ◽  
Chenglong Li ◽  
Jiayuh Lin
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Small Molecule ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Inhibitory Effects ◽  
Stat3 Signaling ◽  
Stat3 Phosphorylation

Ovarian cancer is the fifth most common cause of cancer deaths among American women. Platinum and taxane combination chemotherapy represents the first-line approach for ovarian cancer, but treatment success is often limited by chemoresistance. Therefore, it is necessary to find new drugs to sensitize ovarian cancer cells to chemotherapy. Persistent activation of Signal Transducer and Activator of Transcription 3 (STAT3) signaling plays an important role in oncogenesis. Using a novel approach called advanced multiple ligand simultaneous docking (AMLSD), we developed a novel nonpeptide small molecule, LLL12B, which targets the STAT3 pathway. In this study, LLL12B inhibited STAT3 phosphorylation (tyrosine 705) and the expression of its downstream targets, which are associated with cancer cell proliferation and survival. We showed that LLL12B also inhibits cell viability, migration, and proliferation in human ovarian cancer cells. LLL12B combined with either paclitaxel or with cisplatin demonstrated synergistic inhibitory effects relative to monotherapy in inhibiting cell viability and LLL12B-paclitaxel or LLL12B-cisplatin combination exhibited greater inhibitory effects than cisplatin-paclitaxel combination in ovarian cancer cells. Furthermore, LLL12B-paclitaxel or LLL12B-cisplatin combination showed more significant in inhibiting cell migration and growth than monotherapy in ovarian cancer cells. In summary, our results support the novel small molecule LLL12B as a potent STAT3 inhibitor in human ovarian cancer cells and suggest that LLL12B in combination with the current front-line chemotherapeutic drugs cisplatin and paclitaxel may represent a promising approach for ovarian cancer therapy.

scholarly journals A novel small molecule LLL12B inhibits STAT3 signaling and sensitizes ovarian cancer cell to paclitaxel and cisplatin

2020 ◽  
Author(s):  
Ruijie Zhang ◽  
Xiaozhi Yang ◽  
Dana M. Roque ◽  
Chenglong Li ◽  
Jiayuh Lin
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Small Molecule ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Inhibitory Effects ◽  
Stat3 Signaling ◽  
Stat3 Phosphorylation

AbstractOvarian cancer is the fifth most common cause of cancer deaths among American women. Platinum and taxane combination chemotherapy represents the first-line approach for ovarian cancer, but treatment success is often limited by chemoresistance. Therefore, it is necessary to find new drugs to sensitize ovarian cancer cells to chemotherapy. Persistent activation of Signal Transducer and Activator of Transcription 3 (STAT3) signaling plays an important role in oncogenesis. Using a novel approach called advanced multiple ligand simultaneous docking (AMLSD), we developed a novel nonpeptide small molecule, LLL12B, which targets the STAT3 pathway. In this study, LLL12B inhibited STAT3 phosphorylation (tyrosine 705) and the expression of its downstream targets, which are associated with cancer cell proliferation and survival. We showed that LLL12B also inhibits cell viability, migration, and proliferation in human ovarian cancer cells. LLL12B combined with either paclitaxel or with cisplatin demonstrated synergistic inhibitory effects relative to monotherapy in inhibiting cell viability and LLL12B-paclitaxel or LLL12B-cisplatin combination exhibited greater inhibitory effects than cisplatin- paclitaxel combination in ovarian cancer cells. Furthermore, LLL12B-paclitaxel or LLL12B-cisplatin combination showed more significant in inhibiting cell migration and growth than monotherapy in ovarian cancer cells. In summary, our results support the novel small molecule LLL12B as a potent STAT3 inhibitor in human ovarian cancer cellsand suggest that LLL12B in combination with the current front-line chemotherapeutic drugs cisplatin and paclitaxel may represent a promising approach for ovarian cancer therapy.

Synthetic Naphthoflavonoids Showing Inhibitory Effects on Clonogenicity against Cisplatin-Resistant A2780/Cis Human Ovarian Cancer Cells

2015 ◽  
Vol 12 (8) ◽  
pp. 628-639
Author(s):  
Yearam Jung ◽  
Soon Young Shin ◽  
Yeonjoong Yong ◽  
Hyuk Yoon ◽  
Seunghyun Ahn ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Inhibitory Effects

scholarly journals CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2745
Author(s):  
Miran Jeong ◽  
Yi-Yue Wang ◽  
Ju-Yeon Choi ◽  
Myong-Cheol Lim ◽  
Jung-Hye Choi
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Cancer Cell Invasion ◽  
Cc Chemokine ◽  
Chemokine Ligand

In the tumor microenvironment, macrophages have been suggested to be stimulated by tumor cells, becoming tumor-associated macrophages that promote cancer development and progression. We examined the effect of these macrophages on human ovarian cancer cell invasion and found that conditioned medium of macrophages stimulated by ovarian cancer cells (OC-MQs) significantly increased cell invasion. CC chemokine ligand 7 (CCL7) expression and production were significantly higher in OC-MQs than in the control macrophages. Peritoneal macrophages from patients with ovarian cancer showed higher CCL7 expression levels than those from healthy controls. Inhibition of CCL7 using siRNA and neutralizing antibodies reduced the OC-MQ-CM-induced ovarian cancer cell invasion. CC chemokine receptor 3 (CCR3) was highly expressed in human ovarian cancer cells, and a specific inhibitor of this receptor reduced the OC-MQ-CM-induced invasion. Specific signaling and transcription factors were associated with enhanced CCL7 expression in OC-MQs. CCL7-induced invasion required the expression of matrix metalloproteinase 9 via activation of extracellular signal-related kinase signaling in human ovarian cancer cells. These data suggest that tumor-associated macrophages can affect human ovarian cancer metastasis via the CCL7/CCR3 axis.

scholarly journals Anticancer Effects of Cordyceps Militaris Extract in Human Ovarian Cancer Cells via ADORA2B (P05-012-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
So Young Yoon ◽  
Soo Jung Park ◽  
Yoon Jung Park
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cordyceps Militaris ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Camp Production ◽  
Anticancer Effects ◽  
Sch 58261

Abstract Objectives The study was aimed to determine anticancer effects of Cordyceps militaris extract (CME) and its major bioactive compound, cordycepin, in human ovarian cancer cells, and to identify their putative molecular mechanism mediated by adenosine receptors (ADORAs). Methods CME was prepared in 50% ethanol solution. LC-MS was used for quantification and Q-TOF MS for qualifying bioactive compounds in CME. MTT assay was performed for cell viability in A2780, SKOV-3, TOV112D, and OVCAR-3 human ovarian cancer cell lines. cAMP response element (CRE)-luciferase reporter gene assays were used to determine whether antitumorigenic effect of CME/cordycepin is based on adenosine derivatives. Additionally, the involvement of ADORA signaling pathway was measured using with ADORA2A antagonist SCH 58261 and ADORA2B antagonist PSB 603. Results Cordycepin concentrations of CME was 21.8%. CME was effective to reduce cell viability in A2780 and OVCAR-3 with IC50 115.2 μg/ml and 155.94 μg/ml respectively, while SKOV-3 and TOV112D were relatively resistant to CME. cAMP production was significantly increased by treatment with cordycepin and, lesser extent, with CME. Among the four types of ADORAs, ADORA2A and 2B showed relatively higher expression levels in ovarian cancer cells. The cAMP production by CME was ameliorated by PSB 603, not SCH 58261, treatment. Conclusions CME and cordycepin have anticancer effects in human ovarian cancer cells via ADORA2B-cAMP pathway. Funding Sources NRF of Korea (2017R1D1A1B03034936 & 22A20130012143) and Health Fellowship Foundation.

scholarly journals LHRH might act as a negative autocrine regulator of proliferation of human ovarian cancer

2000 ◽  
pp. 665-670 ◽  
Author(s):  
G Emons ◽  
S Weiss ◽  
O Ortmann ◽  
C Grundker ◽  
KD Schulz
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Lhrh Agonists ◽  
Ovarian Cancer Cell Lines ◽  
Low Concentrations

OBJECTIVE: More than 80% of human ovarian cancers express LHRH and its receptor. The proliferation of human ovarian cancer cell lines is reduced by both LHRH agonists and antagonists. This study was designed to further clarify the possible biological function of this LHRH system. DESIGN: As LHRH agonists and antagonists uniformly reduce proliferation of human ovarian cancer in a dose-dependent way, the effect of low concentrations of authentic LHRH was studied. In addition, longer periods of treatment (up to 9 days) were analyzed. To assess the physiological role of LHRH produced by ovarian cancer cells it was neutralized by adequate concentrations of a specific LHRH antiserum. METHODS: Human ovarian cancer cells EFO-21 and EFO-27, which express LHRH and its receptor, were incubated for 1-9 days with increasing concentrations (1pmol/l to 10 micromol/l) of authentic LHRH or with concentrations of LHRH antiserum capable of neutralizing at least 1nmol/l LHRH. Proliferation was assessed by counting cells. RESULTS AND CONCLUSIONS: Authentic LHRH reduced time- and dose-dependently proliferation (by maximally mean+/-s.e.m. 32.7 +/- 4.4%, Newman-Keuls, P < 0.001) of both ovarian cancer cell lines. At very low concentrations (1pmol/l) a marginal reduction of proliferation or no effect was observed. A mitogenic effect of authentic LHRH was never detected. Treatment of ovarian cancer cell cultures with antiserum to LHRH significantly increased (up to mean+/-s.e.m. 121.0 +/- 2.8% of controls, Newman-Keuls P <0.001) proliferation of EFO-21 and EFO-27 cells. These findings suggest that LHRH produced by human ovarian cancer cells might act as a negative autocrine regulator of proliferation.

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

2016 ◽  
Vol 64 (4) ◽  
pp. 950.1-950 ◽  
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.

scholarly journals NDRG2 gene expression pattern in ovarian cancer and its specific roles in inhibiting cancer cell proliferation and suppressing cancer cell apoptosis

2020 ◽  
Author(s):  
Fenhong Kang ◽  
Yanlong Wang ◽  
Yaping Luo ◽  
Yongjun Zhang
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Colony Formation ◽  
G1 Phase ◽  
Ovarian Cancer Cells ◽  
Cycle Arrest

Abstract Background: The cancer cell metastasis and the acquisition of chemotherapy resistance remain huge challenge for ovarian cancer treatment. Previously, N-myc downstream-regulated gene 2 (NDRG2) serves as a tumor suppressor for many cancers. Here, we attempted to investigate the specific roles of NDRG2 in ovarian cancer. Methods: The expression levels of NDRG2 were detected by qRT-PCR or Immunoblotting. CCK-8 assay was employed to examine the cell viability of ovarian cancer cells. The colony formation ability was determined by colony formation assay. Flow cytometry analyses were performed to detect the cell apoptosis and cell cycle. Xenograft tumor assay was performed to detect the in vivo function of NDRG2. Results: We revealed that NDRG2 mRNA expression and protein levels were downregulated within both ovarian cancer tissues and cell lines. The overexpression of NDRG2 dramatically inhibited the cell viability and colony formation and tumor growth, whereas promoted the cell apoptosis, cell cycle arrest in G1 phase within ovarian cancer cells. More importantly, NDRG2 overexpression significantly enhanced the suppressive roles of cisplatin (DDP) in ovarian cancer cell viability. On the contrary, NDRG2 silence exerted opposing effects on ovarian cancer cells. Conclusions: In summary, we provide a solid experimental basis demonstrating the tumor-suppressive effects of NDRG2 in inhibiting the cell proliferation, enhancing the cell apoptosis, eliciting the cell cycle arrest in G1 phase, and promoting the suppressive effects of DDP on the viability of ovarian cancer cells. NDRG2 administration presents a potent adjuvant treatment for ovarian cancer therapy.

scholarly journals NCX-4016, a nitro-derivative of aspirin, inhibits EGFR and STAT3 signaling and mdulates Bcl-2 proteins in cisplatin-resistant human ovarian cancer cells and xenografts

Cell Cycle ◽  
2008 ◽  
Vol 7 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Karuppaiyah Selvendiran ◽  
Anna Bratasz ◽  
Liyue Tong ◽  
Louis J. Ignarro ◽  
Periannan Kuppusamy
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Nitro Derivative ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Stat3 Signaling ◽  
Ncx 4016

scholarly journals NDRG2 gene expression pattern in ovarian cancer and its specific roles in inhibiting cancer cell proliferation and suppressing cancer cell apoptosis

2020 ◽  
Author(s):  
Fenhong Kang ◽  
Yanlong Wang ◽  
Yaping Luo ◽  
Yongjun Zhang
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Colony Formation ◽  
G1 Phase ◽  
Ovarian Cancer Cells ◽  
Cycle Arrest

Abstract Background The cancer cell metastasis and the acquisition of chemotherapy resistance remain huge challenge for ovarian cancer treatment. Previously, N-myc downstream-regulated gene 2 (NDRG2) serves as a tumor suppressor for many cancers. Here, we attempted to investigate the specific roles of NDRG2 in ovarian cancer.Methods The expression levels of NDRG2 were detected by qRT-PCR or Immunoblotting assay. CCK-8 assay was employed to examine the cell viability of ovarian cancer cells. The colony formation ability was determined by colony formation assay. Flow cytometry analyses were performed to detect the cell apoptosis and cell cycle.Results Herein, we revealed that NDRG2 mRNA expression and protein levels were downregulated within both ovarian cancer tissues and cell lines. The overexpression of NDRG2 dramatically inhibited the cell viability and colony formation, whereas promoted the cell apoptosis and cell cycle arrest in G1 phase within ovarian cancer cells. More importantly, NDRG2 overexpression significantly enhanced the suppressive roles of cisplatin (DDP) in ovarian cancer cell viability. On the contrary, NDRG2 silence exerted opposing effects on ovarian cancer cells.Conclusions In summary, we provide a solid experimental basis demonstrating the tumor-suppressive effects of NDRG2 in inhibiting the cell proliferation, enhancing the cell apoptosis, eliciting the cell cycle arrest in G1 phase, and promoting the suppressive effects of DDP on the viability of ovarian cancer cells. NDRG2 administration presents a potent adjuvant treatment for ovarian cancer therapy, which needs further in vivo and clinical investigation.

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