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

10.21203/rs.2.20090/v2 ◽

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.

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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

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v20i2.9 ◽

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.

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δ‐Tocotrienol sensitizes and re‐sensitizes ovarian cancer cells to cisplatin via induction of G1 phase cell cycle arrest and ROS/MAPK‐mediated apoptosis

Cell Proliferation ◽

10.1111/cpr.13111 ◽

2021 ◽

Author(s):

Fabrizio Fontana ◽

Monica Marzagalli ◽

Michela Raimondi ◽

Valentina Zuco ◽

Nadia Zaffaroni ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Phase Cell ◽

G1 Phase ◽

Ovarian Cancer Cells ◽

Cycle Arrest

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Effects of alisol B 23-acetate on ovarian cancer cells: G1 phase cell cycle arrest, apoptosis, migration and invasion inhibition

Phytomedicine ◽

10.1016/j.phymed.2016.04.003 ◽

2016 ◽

Vol 23 (8) ◽

pp. 800-809 ◽

Cited By ~ 28

Author(s):

Le-Le Zhang ◽

Yu-Lian Xu ◽

Zheng-Hai Tang ◽

Xiao-Huang Xu ◽

Xin Chen ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Phase Cell ◽

G1 Phase ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Cycle Arrest ◽

Invasion Inhibition

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

International Journal of Molecular Sciences ◽

10.3390/ijms22095022 ◽

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.

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

10.21203/rs.3.rs-639116/v1 ◽

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.

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Evaluation of The Antiproliferative Effect of Iso-Mukaadial Acetate on Breast and Ovarian Cancer Cells

10.21203/rs.3.rs-639116/v2 ◽

2021 ◽

Author(s):

Portia Raphela-Choma ◽

Mthokozisi Simelane ◽

Mpho 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.

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

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:206-210 ◽

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.

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

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190118113201 ◽

2019 ◽

Vol 19 (4) ◽

pp. 473-486 ◽

Cited By ~ 1

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.

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