scholarly journals Anticancer effect of 7-hydroxycoumarin in cisplatin-resistant ovarian cancer cell is mediated via apoptosis induction, caspase activation and cell cycle arrest at G2M phase

2022 ◽  
Vol 20 (2) ◽  
pp. 281-286
Author(s):  
Hongmei Wang ◽  
Yina Wang
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Anticancer Effect ◽  
Cycle Arrest

Purpose: To investigate the anticancer effects of 7-hydroxycoumarin against cisplatin-resistant ovarian cancer cell line, and the underlying mechanism(s). Methods: Cell proliferation was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The 4’,6-diamidino-2-phenylindole (DAPI) and acridine orange/ethidium bromide (AO/EB) dual staining methods were used for measuring cell apoptosis in terms of DNA damage. Flow cytometry was used for analysis of mitosis of cancer cells, while protein expression levels were assayed with western blotting. Results: The 7-hydroxycoumarin preferentially inhibited the proliferation of the ovarian cancer cells, but had significantly less prominent effects on normal cells (p < 0.05). The decrease in cell proliferation was due to induction of cell apoptosis via caspase-linked apoptotic pathway. Treatment with 7- hdoxycoumarin further led to the arrest of cancer cell cycle at G2/M stage (p < 0.05) via down-regulation of the expressions of regulatory proteins that promote mitotic entry. Conclusion: 7-Hydroxycoumarin exerts significant anticancer effect against cisplatin-resistant ovarian cancer cells via decrease in cell proliferation, induction of apoptosis and mitotic cell cycle arrest. Thus, the compound could emerge as a vital lead molecule in the treatment of cisplatin-resistant type of human ovarian cancer.

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 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.

scholarly journals Follicle-Stimulating Hormone Is an Autocrine Regulator of the Ovarian Cancer Metastatic Niche Through Notch Signaling

2018 ◽  
Vol 3 (2) ◽  
pp. 340-357 ◽  
Author(s):  
Sakshi Gera ◽  
Sandeep Kumar S. ◽  
Shalini N Swamy ◽  
Rahul Bhagat ◽  
Annapurna Vadaparty ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Notch Signaling ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Fsh Receptor ◽  
Ovarian Cancer Cell Lines ◽  
Tumor Tissues

Abstract The association between the upregulated Notch and FSH signaling and ovarian cancer is well documented. However, their signaling has been investigated independently and only in the primary tumor tissues. The aim of this study was to investigate the interactive effects of FSH and Notch signaling on ovarian cancer proliferation, formation, and maintenance of disseminated ovarian cancer cells. The roles of Notch and FSH in ovarian cancer pathogenesis were investigated with ovarian cancer cell lines and specific antibodies against Notch and FSH receptor (FSHR). FSH upregulated Notch signaling and proliferation in ovarian cancer cells. High levels of FSH were detected in the ascites of patients with serous ovarian adenocarcinoma. Spheroids from the patients’ ascites, as well as the spheroids from ovarian cancer cell lines under low attachment culture conditions, expressed FSHβ subunit mRNA and secreted the hormone into the medium. In contrast, primary ovarian tumor tissues and cell line monolayers expressed very low levels of FSHβ. Ovarian cancer cell spheroids also exhibited higher expression of FSH receptor and Notch downstream genes than their monolayer counterparts. A combination of FSHR and Notch antagonistic antibodies significantly inhibited spheroid formation and cell proliferation in vitro. This study demonstrates that spheroids in ascites express and secrete FSH, which regulates cancer cell proliferation and spheroidogenesis through Notch signaling, suggesting that FSH is an autocrine regulator of cancer metastasis. Furthermore, Notch and FSHR are potential immunotherapeutic targets for ovarian cancer treatment.

LY294002 and Metformin Cooperatively Enhance the Inhibition of Growth and the Induction of Apoptosis of Ovarian Cancer Cells

2012 ◽  
Vol 22 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Cuilan Li ◽  
Vincent Wing Sun Liu ◽  
David Wai Chan ◽  
Kwok Ming Yao ◽  
Hextan Yuen Sheung Ngan
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Flow Cytometry ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Mtor Pathway ◽  
Ovarian Cancer Cells ◽  
Cancer Cell Growth

BackgroundThe phosphoinositide 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (AKT)/mammalian target of rapamycin (mTOR) pathway is frequently aberrantly activated in ovarian cancer and confers the chemoresistant phenotype of ovarian cancer cells. LY294002 (PI3K inhibitor) and metformin (5′-adenosine monophosphate [AMP]-activated protein kinase [AMPK] activator) are 2 drugs that were known to inhibit mTOR expression through the AKT-dependent and AKT-independent pathways, respectively. In this study, we explored the effectiveness of LY294002 and metformin in combination on inhibition of ovarian cancer cell growth.MethodsWestern blotting was used to detect the changes of PI3K/AKT/mTOR and AMPK/acetyl-CoA carboxylase (ACC) signaling activities, cell cycle control, and apoptosis. Cell growth was evaluated by cell proliferation, colony formation, and soft agar assays. Flow cytometry was used to study cell cycle distribution and cell death upon drug treatment.ResultsOur study showed that LY294002 and metformin in combination could simultaneously enhance the repression of the PI3K/AKT/mTOR pathway and the activation of the AMPK/ACC pathway. The downstream target of AKT and AMPK, mTOR, was cooperatively repressed when the drugs were used together. The cell cycle regulatory factors, p53, p27, and p21, were up-regulated. On the other hand, caspase 3 and poly (ADP-ribose) polymerase activities involved in apoptosis were also activated. Cell growth assays indicated that LY294002 and metformin could effectively inhibit ovarian cancer cell growth. Flow cytometry analysis showed that the treatment of the 2 drugs mentioned above induced cell cycle arrest at G1 phase and increased sub-G1 apoptotic cells.ConclusionThe combinational use of LY294002 and metformin can enhance inhibition of the growth and induction of the apoptosis of ovarian cancer cells. Our results may provide significant insight into the future therapeutic regimens in ovarian cancer.

scholarly journals Trichodermin Induces G0/G1 Cell Cycle Arrest by Inhibiting c-Myc in Ovarian Cancer Cells and Tumor Xenograft-Bearing Mice

2021 ◽  
Vol 22 (9) ◽  
pp. 5022
Author(s):  
Ying Gao ◽  
Sarah L. Miles ◽  
Piyali Dasgupta ◽  
Gary O. Rankin ◽  
Stephen Cutler ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest

Ovarian cancer is a fatal gynecological cancer because of a lack of early diagnosis, which often relapses as chemoresistant. Trichodermin, a trichothecene first isolated from Trichoderma viride, is an inhibitor of eukaryotic protein synthesis. However, whether trichodermin is able to suppress ovarian cancer or not was unclear. In this study, trichodermin (0.5 µM or greater) significantly decreased the proliferation of two ovarian cancer cell lines A2780/CP70 and OVCAR-3. Normal ovarian IOSE 346 cells were much less susceptible to trichodermin than the cancer cell lines. Trichodermin predominantly inhibited ovarian cancer cells by inducing G0/G1 cell cycle arrest rather than apoptosis. Trichodermin decreased the expression of cyclin D1, CDK4, CDK2, retinoblastoma protein, Cdc25A, and c-Myc but showed little effect on the expression of p21Waf1/Cip1, p27Kip1, or p16Ink4a. c-Myc was a key target of trichodermin. Trichodermin regulated the expression of Cdc25A and its downstream proteins via c-Myc. Overexpression of c-Myc attenuated trichodermin’s anti-ovarian cancer activity. In addition, trichodermin decelerated tumor growth in BALB/c nude mice, proving its effectiveness in vivo. These findings suggested that trichodermin has the potential to contribute to the treatment of ovarian cancer.

scholarly journals Evaluation of the antiproliferative effect of Iso-mukaadial acetate on breast and ovarian cancer cells

2021 ◽  
Author(s):  
Portia P Raphela-Choma ◽  
Mthokozisi BC Simelane ◽  
Mpho S Choene
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Breast And Ovarian Cancer ◽  
Cycle Arrest

Abstract Background Natural compounds derived from various medicinal plants may activate several physiological pathways which can be valuable to diseases such as cancer. Isomukaadial acetate has previously been shown to possess antimalarial and anti-diabetic properties. The purpose of this study was to evaluate the antiproliferative effects of isomukaadial acetate on breast and ovarian cancer cell lines. Method Cell viability assays were conducted using AlamarBlue assay and xCELLigence system. Cell apoptosis and cell cycle arrest were determined and analyzed by flow cytometer. Effector caspase (3/7) activation was evaluated by caspase Glo®-3/7 reagent and gene expression was analyzed by Real-Time Polymerase Chain Reaction. Results The Alamar blue assay and xCELLigence showed that Iso-mukaadial acetate exhibited anti-proliferative effects on MDA-MB 231, RMG-1, and HEK 293 cell lines in a concentration-dependent manner. Iso-mukaadial acetate induced apoptosis in both cancer cell lines caused cell cycle arrest at the S phase (RMG-1) and early G2 phase (MDA-MB 231) and expressed caspase 3/7 activity in MDA-MB 231 and RMG-1 cells. BAX and p21 were upregulated in MDA-MB 231 and RMG-1 cells after treatment. Conclusion IMA significantly inhibited cancer growth and induced cell apoptosis with cell cycle modulation. IMA may be considered a promising candidate for the development of anticancer drugs either for its cytotoxic or cytostatic effect Furthermore, IMA requires to be further studied more to clearly understand its mechanism of action on cancer cells.

scholarly journals Inhibition of ALDH1A1 Activity in Cisplatin-Resistant Ovarian Cancer Cells Alters Their Cancer Stemness, Cell Cycle Profile and Mitochondrial Respiration Rate

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1023-A1024
Author(s):  
Ilangovan Ramachandran ◽  
Sivakumar Ramadoss ◽  
Suvajit Sen ◽  
Selvendiran Karuppaiyah ◽  
R Ileng Kumaran ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Mitochondrial Respiration ◽  
Ovarian Cancer Cells ◽  
Cancer Stemness ◽  
Cycle Arrest ◽  
Anticancer Effects ◽  
Chemoresistant Ovarian Cancer

Abstract Introduction: Ovarian cancer is one of the leading cause of morbidity and death among women, with a five-year relative survival rate of only 30% in patients diagnosed with distant metastasis. The ovarian cancer cells initially respond to first-line platinum drug cisplatin [cis-diamminedichloroplatinum(II) (CDDP)] treatment. But, they subsequently develop resistance to CDDP and eventually exhibit chemoresistance. Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) is one of the key functional markers of ovarian cancer stem cells (CSCs) that confers cancer stemness and therapeutic resistance, and is associated with poor prognosis and patient survival. In this study, we have assessed the anticancer effects of the ALDH1A1 inhibitor, A37, in CDDP-resistant ovarian cancer cells in vitro. Experimental Methods: SK-OV-3-CDDP, cisplatin-resistant ovarian cancer cells were treated with different concentrations of the small molecule inhibitor of ALDH1A1, A37. We determined the cell proliferation using water-soluble tetrazolium salt (WST-1) assay at 24 and 48 h. The distribution of cell division phases by cell cycle analysis and oxygen consumption rate (OCR) via seahorse extracellular flux analysis were assessed by flow cytometry and seahorse XFe24 analyzer, respectively. Furthermore, we examined the protein expression of key signaling molecules by western blot analysis and cancer stemness by tumorsphere formation assay. Results: Treatment of SK-OV-3-CDDP cells with A37 significantly reduced the ovarian cancer cell proliferation. Interestingly, A37 induced cell cycle arrest as observed by an increase in G1 phase of the cell cycle. Additionally, A37 reduced the mitochondrial respiration of ovarian cancer cells as observed by the decrease in basal OCR. Moreover, A37 treatment markedly decreased the expression of WW domain containing transcription regulator 1 (WWTR1) protein [also called as transcriptional co-activator with PDZ-binding motif (TAZ)], which is a key downstream effector of mammalian Hippo signaling pathway that promotes cancer stemness, metastasis and chemoresistance. Importantly, A37 reduced the number and size of the tumorspheres. Conclusions: Our study suggests that inhibiting the ALDH1A1 activity using A37 reduced the cell proliferation and induced cell cycle arrest in CDPP-resistant ovarian cancer cells. The mechanism by which A37 elicits its anticancer effects on ovarian cancer cells include impairment in mitochondrial respiration that could alter cancer cell metabolism, and a decrease in WWTR1/TAZ expression and tumorsphere formation that could suppress cancer stemness. Our findings demonstrate that inhibition of ALDH1A1 could effectively eliminate the chemoresistant ovarian cancer cells, and therefore, new strategies targeting ALDH1A1 could lead to the development of novel therapeutics for aggressive chemoresistant ovarian cancer.

scholarly journals Dezocine inhibits cell proliferation, migration and invasion by targeting CRABP2 in ovarian cancer

2020 ◽  
Author(s):  
Chuanfeng Zhang ◽  
Ruirui Pan ◽  
Shuangshuang Ma ◽  
Shoucai Xu ◽  
Baosheng Wang
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Metastatic Potential ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Mechanism Study ◽  
Skov3 Cells

Abstract Background Previous studies have shown that some anesthesia drugs can inhibit tumor growth and metastasis. As a clinical anesthetic drug, dezocine has been reported to play an important role in immune function. However, the effects of dezocine on ovarian cancer cell growth and metastasis are not fully understood. Results In this study, we found that dezocine dose-dependently inhibited the viability of ES-2 and SKOV3 cells. Dezocine suppressed the migration and invasion abilities of ovarian cancer cells, and promoted apoptosis. Moreover, the Akt/mTOR signaling pathway was also inhibited by dezocine. Furthermore, mechanism study showed that dezocine could significantly inhibited the expression of CRABP2, and CRABP2 overexpression reversed the inhibitory effects of dezocine on ovarian cancer cell proliferation and migration. Conclusion In conclusion, dezocine has significant anti-tumor effects on the growth and metastatic potential of ovarian cancer cells, and CRABP2 functions as a downstream effector of dezocine.

Abstract 4087: ALDH1A1 inhibitor induces cell cycle arrest and reduces cell proliferation of cisplatin-resistant ovarian cancer cells

2020 ◽  
Author(s):  
Ilangovan Ramachandran ◽  
Sivakumar Ramadoss ◽  
Selvendiran Karuppaiyah ◽  
Lauren Nathan ◽  
R. Ileng Kumaran ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Cycle Arrest

miR-194 Inhibits Ovarian Cancer Cell Proliferation and Reduces Cisplatin Resistance by Targeting Yes-Associated Protein

2020 ◽  
Vol 10 (8) ◽  
pp. 1170-1175
Author(s):  
Hao Tang ◽  
Ping Gong ◽  
Ling Tao ◽  
Yurong Hua
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Ovarian Cancer Cell ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Ovarian Cancer Cells ◽  
Cancer Cell Proliferation ◽  
Elevated Expression

Elevated expression of Yes-associated protein (YAP1) is associated with ovarian cancer. Bioinformatics analysis showed a relationship between miR-194 and YAP1. Our study intends to assess whether miR-194 regulates YAP1 expression and affects the proliferation of ovarian cancer cells and CDDP resistance. CDDP-resistant cell line A2780/CDDP was established and the expression of miR-194 and YAP1 in parental A2780 cells and normal ovarian epithelial IOSE80 cells were compared. A2780/CDDP cells were separated into miR-NC group and miR-194 mimic group followed by analysis of miR-194 and YAP1 expression, and cell apoptosis and proliferation by flow cytometry. There was a targeted relationship between miR-194 and YAP1 mRNA. A2780/CDDP cells had the lowest miR-194 expression followed by A2780 cells and IOSE80 cells. In addition, YAP1 level was highest in A2780/CDDP cells followed by A2780 cells and IOSE80 cells. Compared with miR-NC group, miR-194 expression was significantly increased in miR-194 mimic transfection group and YAP1 protein expression was significantly decreased, with increased cell apoptosis and reduced cell proliferation ability. Decreased miR-194 expression and increased YAP1 expression are related to ovarian cancer CDDP resistance. Increased miR-194 can down-regulate YAP1, inhibit ovarian cancer cell proliferation, promote cell apoptosis, and reduce CDDP resistance.

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