Starving Tumors: Inhibition of Glycolysis Reduces Viability of Human Endometrial and Ovarian Cancer Cells and Enhances Antitumor Efficacy of GnRH Receptor-Targeted Therapies

2013 ◽  
Vol 23 (1) ◽  
pp. 34-40 ◽  
Author(s):  
Madita Reutter ◽  
Günter Emons ◽  
Carsten Gründker
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Targeted Therapies ◽  
Caspase 3 ◽  
Single Agent ◽  
Gnrh Receptor ◽  
Ovarian Cancer Cells ◽  
Inhibition Of Glycolysis ◽  
Induction Of Apoptosis ◽  
Glycolysis Inhibitor

ObjectiveIncreased glycolysis for energy production is necessary for survival of tumor cells and thus represents a selective therapeutic target. We have analyzed in vitro whether inhibition of glycolysis can reduce the viability of human endometrial and ovarian cancer cells and whether it can enhance the antitumor efficacy of GnRH receptor-targeted therapies.Materials and MethodsCell viability of ovarian and endometrial cancer cells treated without or with glycolysis inhibitor 2-Deoxy-D-Glucose (2DG) alone or in combination with GnRH-II antagonist [Ac-D2Nal1, D-4Cpa2, D-3Pal3,6,Leu8, D-Ala10]GnRH-II or with cytotoxic GnRH-I agonist AEZS-108 (AN-152) was measured using alamar blue assay. Induction of apoptosis was analyzed using TUNEL assay and quantified by measurement of loss of mitochondrial membrane potential. Apoptotic signaling was measured by quantification of activated caspase-3 by using the Western blot technique.ResultsTreatment of endometrial and ovarian cancer cells with glycolysis inhibitor 2DG resulted in a significant decrease of cell viability and a significant increase of apoptosis. Treatment with 2DG in combination with the GnRH-II antagonist or with AEZS-108 resulted in a significant reduced viability compared with single-agent treatments. The observed reduction in viability was due to induction of apoptosis. Also for apoptosis induction, a significant stronger effect in the case of cotreatments compared with single-agent treatments could be observed. These additive effects could be correlated to increased activation of caspase-3.ConclusionsThe glycolytic phenotype of human endometrial and ovarian cancer cells can be targeted for therapeutic intervention. In addition, cotreatment of a glycolysis inhibitor with GnRH receptor-targeted therapies might be a suitable therapy for GnRH receptor-positive human endometrial and ovarian cancers.

scholarly journals Clerodane Diterpenoids from an Edible Plant Justicia insularis: Discovery, Cytotoxicity, and Apoptosis Induction in Human Ovarian Cancer Cells

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5933
Author(s):  
Idowu E. Fadayomi ◽  
Okiemute R. Johnson-Ajinwo ◽  
Elisabete Pires ◽  
James McCullagh ◽  
Tim D. W. Claridge ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Dependent Manner ◽  
Edible Plant ◽  
Cytotoxic Compounds ◽  
Clerodane Diterpenoids ◽  
Induction Of Apoptosis

Objectives: The toxicity of chemotherapeutic anticancer drugs is a serious issue in clinics. Drug discovery from edible and medicinal plants represents a promising approach towards finding safer anticancer therapeutics. Justicia insularis T. Anderson (Acanthaceae) is an edible and medicinal plant in Nigeria. This study aims to discover cytotoxic compounds from this rarely explored J. insularis and investigate their underlying mechanism of action. Methods: The cytotoxicity of the plant extract was evaluated in human ovarian cancer cell lines and normal human ovarian surface epithelia (HOE) cells using a sulforhodamine B assay. Bioassay-guided isolation was carried out using column chromatography including HPLC, and the isolated natural products were characterized using GC-MS, LC-HRMS, and 1D/2D NMR techniques. Induction of apoptosis was evaluated using Caspase 3/7, 8, and 9, and Annexin V and PI based flow cytometry assays. SwissADME and SwissTargetPrediction web tools were used to predict the molecular properties and possible protein targets of identified active compounds. Key finding: The two cytotoxic compounds were identified as clerodane diterpenoids: 16(α/β)-hydroxy-cleroda-3,13(14)Z-dien-15,16-olide (1) and 16-oxo-cleroda-3,13(14)E-dien-15-oic acid (2) from the Acanthaceous plant for the first time. Compound 1 was a very abundant compound (0.7% per dry weight of plant material) and was shown to be more potent than compound 2 with IC50 values in the micromolar range against OVCAR-4 and OVCAR-8 cancer cells. Compounds 1 and 2 were less cytotoxic to HOE cell line. Both compounds induced apoptosis by increasing caspase 3/7 activities in a concentration dependent manner. Compound 1 further increased caspase 8 and 9 activities and apoptosis cell populations. Compounds 1 and 2 are both drug like, and compound 1 may target various proteins including a kinase. Conclusions: Clerodane diterpenoids (1 and 2) in J. insularis were identified as cytotoxic to ovarian cancer cells via the induction of apoptosis, providing an abundant and valuable source of hit compounds for the treatment of ovarian cancer.

scholarly journals Isoflavones Isolated from the Seeds of Millettia ferruginea Induced Apoptotic Cell Death in Human Ovarian Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 207 ◽  
Author(s):  
Yi-Yue Wang ◽  
Jun Hyeok Kwak ◽  
Kyung-Tae Lee ◽  
Tsegaye Deyou ◽  
Young Pyo Jang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Millettia Ferruginea ◽  
Induced Apoptosis

The seeds of Millettia ferruginea are used in fishing, pesticides, and folk medicine in Ethiopia. Here, the anti-cancer effects of isoflavones isolated from M. ferruginea were evaluated in human ovarian cancer cells. We found that isoflavone ferrugone and 6,7-dimethoxy-3’,4’-methylenedioxy-8-(3,3-dimethylallyl)isoflavone (DMI) had potent cytotoxic effects on human ovarian cancer cell A2780 and SKOV3. Ferrugone and DMI treatment increased the sub-G1 cell population in a dose-dependent manner in A2780 cells. The cytotoxic activity of ferrugone and DMI was associated with the induction of apoptosis, as shown by an increase in annexin V-positive cells. Z-VAD-fmk, a broad-spectrum caspase inhibitor, and z-DEVD-fmk, a caspase-3 inhibitor, significantly reversed both the ferrugone and DMI-induced apoptosis, suggesting that cell death stimulated by the isoflavones is mediated by caspase-3-dependent apoptosis. Additionally, ferrugone-induced apoptosis was found to be caspase-8-dependent, while DMI-induced apoptosis was caspase-9-dependent. Notably, DMI, but not ferrugone, increased the intracellular levels of reactive oxygen species (ROS), and antioxidant N-acetyl-L-cysteine (NAC) attenuated the pro-apoptotic activity of DMI. These data suggest that DMI induced apoptotic cell death through the intrinsic pathway via ROS production, while ferrugone stimulated the extrinsic pathway in human ovarian cancer cells.

scholarly journals IP10-CDR3 Reduces The Viability And Induces The Apoptosis Of Ovarian Cancer Cells By Down-Regulating The Expression Of Bcl-2 And Caspase 3

2019 ◽  
Vol Volume 12 ◽  
pp. 9697-9706
Author(s):  
Qi Chen ◽  
Quan He ◽  
Lingling Zhuang ◽  
Kunya Wang ◽  
Chunhua Yin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Ovarian Cancer Cells

Induction of apoptosis in human ovarian cancer cells by new anticancer compounds, epothilone A and B

2013 ◽  
Vol 27 (1) ◽  
pp. 239-249 ◽  
Author(s):  
Aneta Rogalska ◽  
Agnieszka Marczak ◽  
Arkadiusz Gajek ◽  
Marzena Szwed ◽  
Agnieszka Śliwińska ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Anticancer Compounds ◽  
Epothilone A ◽  
Induction Of Apoptosis

Platycodon grandiflorum Induces Apoptosis in SKOV3 Human Ovarian Cancer Cells Through Mitochondrial-Dependent Pathway

2010 ◽  
Vol 38 (02) ◽  
pp. 373-386 ◽  
Author(s):  
Qin Hu ◽  
Ruile Pan ◽  
Liwei Wang ◽  
Bo Peng ◽  
Jingtian Tang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cytochrome C ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Ovarian Cancer Cells ◽  
Mitochondrial Cytochrome ◽  
Cytochrome C Release ◽  
Apoptotic Pathway ◽  
Platycodon Grandiflorum ◽  
Mitochondrial Cytochrome C

Platycodon grandiflorum (Jacq.) A. DC., a Chinese food and medicine, has been used as expectorant traditionally. The present study aimed to investigate the effect of Platycodon grandiflorum extract (PGE) on SKOV3 ovarian cancer cells. 3-(4,5- dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay was used to monitor cell numbers, Annexin-V/propidium iodide (PI) staining, RT-PCR and Western blot were used to examine cell apoptosis, caspases activation. Bcl-2 and Bax expressions and mitochondrial cytochrome c release. Our result showed that PGE-induced apoptosis was associated with activation of caspase-3, -8 and -9, down-regulation of Bcl-2, up-regulation of Bax and release of mitochondrial cytochrome c to cytosol. The data indicate that PGE may have anti-tumor effect mainly via caspase-3 and caspase-9 dependent apoptotic pathway.

scholarly journals Caspase-3-dependent Activation of Calcium-independent Phospholipase A2Enhances Cell Migration in Non-apoptotic Ovarian Cancer Cells

2006 ◽  
Vol 281 (39) ◽  
pp. 29357-29368 ◽  
Author(s):  
Xiaoxian Zhao ◽  
Dongmei Wang ◽  
Zhenwen Zhao ◽  
Yingyi Xiao ◽  
Saubhik Sengupta ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Ovarian Cancer Cells

scholarly journals Effect of Ginsenoside Rh-2 via Activation of Caspase-3 and Bcl-2-Insensitive Pathway in Ovarian Cancer Cells

2016 ◽  
pp. 1031-1037 ◽  
Author(s):  
J. H. KIM ◽  
J.-S. CHOI
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Therapeutic Potential ◽  
Future Application ◽  
Ovarian Cancer Cells ◽  
Therapeutic Effects ◽  
Apoptosis Pathway ◽  
Skov3 Cells

Ginsenoside has been reported to have therapeutic effects for some types of cancer, but its effect on ovarian cancer cells has not been evaluated. In this study, we monitored the effects of ginsenoside-Rh2 (Rh2) on the inhibition of cell proliferation and the apoptotic process in the ovarian cancer cell line SKOV3 using an MTT assay and TUNEL assay. We found that Rh2 inhibited cell proliferation and significantly induced apoptosis. We confirmed the apoptotic effects of Rh2 using western blot analysis of apoptosis-related proteins. Specifically, the levels of cleaved poly ADP ribose polymerase (PARP) and cleaved caspase-3 significantly increased in SKOV3 cells treated with Rh2. Therefore, Rh2 clearly suppressed the growth of SKOV3 cells in vitro, which was associated with induction of the apoptosis pathway. Moreover, the migration assay showed that Rh2 inhibited the invasive ability of SKOV3 cells. Taken together, our results suggest that Rh2 has anticancer effects in SKOV3 cells through inhibition of cell proliferation and induction of apoptosis. Considering the therapeutic potential of Rh2, more studies should be carried out to facilitate the future application of this natural product as a potential anti-cancer agent.

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