S-Phase Cell Cycle Arrest, Apoptosis, and Molecular Mechanisms of Aplasia Ras homolog Member I–Induced Human Ovarian Cancer SKOV3 Cell Lines

ObjectiveAplasia Ras homolog member I (ARHI) is associated with human ovarian cancer (HOC) growth and proliferation; however, the mechanisms are unclear. The purpose of this study was to investigateARHIeffects in HOC SKOV3 cells.MethodsWe transfected SKOV3 cells with PIRES2-EGFP-ARHI and measured growth inhibition rates, cell cycle distribution, apoptosis rates, and expression of P-STAT3 (phosphorylated signal transduction and activators of transcription 3) and P-ERK (phosphorylated extracellular signal regulated protein kinase).ResultsOur data showed significant inhibition of growth, significantly increased S-phase arrest and apoptosis rates, and reduction of P-STAT3 and P-ERK1/2 expression levels.ConclusionsWe propose the mechanism may involveARHI-induced phosphorylation of ERK1/2 and STAT3 protein kinases, thereby blocking proliferation signaling pathways, to induce HOC SKOV3 apoptosis.

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The natural terthiophene α-terthienylmethanol induces S phase cell cycle arrest of human ovarian cancer cells via the generation of ROS stress

Chemico-Biological Interactions ◽

10.1016/j.cbi.2017.05.011 ◽

2017 ◽

Vol 272 ◽

pp. 72-79 ◽

Cited By ~ 12

Author(s):

Umma Hafsa Preya ◽

Kyung-Tae Lee ◽

Nam-Jung Kim ◽

Jung-Yun Lee ◽

Dae Sik Jang ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

S Phase ◽

Phase Cell ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Cycle Arrest

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SAR1 Is Critical to the HbF-Inducing Effect of HU and Other Therapeutic Cytotoxic Agents

Blood ◽

10.1182/blood.v118.21.1306.1306 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1306-1306

Author(s):

Jianqiong Zhu ◽

Kyung Chin ◽

Wulin Aerbajinai ◽

Chutima Kumkhaek ◽

Wenli Liu ◽

...

Keyword(s):

Cell Cycle ◽

Molecular Mechanisms ◽

Conflicts Of Interest ◽

Fetal Hemoglobin ◽

K562 Cells ◽

S Phase ◽

Molecular Therapy ◽

Cytotoxic Agents ◽

Phase Cell ◽

Gamma Globin

Abstract Abstract 1306 Hydroxyurea (HU) is a drug that is effectively used in the management of the β-hemoglobinopathies sickle cell disease and β-thalassemia by augmenting the production of fetal hemoglobin (HbF). However, the molecular mechanisms underlying HU-mediated HbF regulation remain unclear, as does the reason why some proportion of the patients failed to show a beneficial therapeutic response. A better understanding of how hydroxyurea acts at the molecule levels and induces fetal hemoglobin production would offer targeted molecular therapy with higher specificity, and less toxicity and may provide alternative effective therapies to current non-responders. Secretion-associated and ras-related protein (SAR1) is a small guanosine triphosphate (GTP)-binding protein that is induced by HU and closely mimics the known effects of HU on erythroid cells, including gamma-globin induction and cell-cycle regulation. Here we report of our further investigation on whether SAR1 is an obligatory mediator to the HbF-inducing effect of HU and other therapeutic cytotoxic agents. Our results indicate that blocking SAR1 expression not only significantly lowered the basal and HU-elicited HbF production in CD34+ and K562 cells (see table), it also abolished HU-mediated S-phase cell-cycle arrest (see table) and cell apoptosis (P<0.001).Transcriptional factor BCL11A, which controls globin switching and suppresses HbF, is involved in SAR1 and HU regulated gamma-globin expression, and SAR1 is required for HU, 5-AZA and Ara-C mediated BCL11A reduction. We also found HU acts through the interaction of NFκB with its conjugated binding site on SAR1 promoter to regulate its transcriptional expression. Our data show that SAR1 is not only sufficient, but indeed necessary and central, to HU's beneficial effects. Our data suggests that SAR1 is not only sufficient, but indeed necessary and central, to HU's erythroid effects. Further exploration of the mechanistic details underlying SAR1 effects may reveal novel therapeutic targets for the beta-globin disorders.MockControl shRNA or microRNASAR1 shRNA or microRNAHU−HU+HU−HU+HU−†pHU+‡pHbF positive CD34 + cells27.00 ± 1.01%50.70 ± 1.88%20.59 ± 0.76%0.00331.77 ± 1.17%0.00001HbF positive K562 cells18.21 ± 0.21%41.00 ± 1.41%19.72 ± 2.11%43.37 ± 0.2%14.29 ± 1.2%0.00426.63 ± 1.23%0.00002Fraction of S-phase cells24.94 ± 0.84%32.38 ± 0.59%24.08 ± 0.59%34.26 ± 0.54%24.88 ± 0.4%0.09727.64 ± 0.25%0.00192†p compared with control HU-‡p compared with control HU+ Disclosures: No relevant conflicts of interest to declare.

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Effect of Juglone on Migration of Human Ovarian Cancer SKOV3 Cells

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.912-914.1911 ◽

2014 ◽

Vol 912-914 ◽

pp. 1911-1914

Author(s):

Liang Zhong Zhao ◽

Shuang Chen ◽

Qing Fang ◽

Duo Zhang ◽

You Peng Zhu ◽

...

Keyword(s):

Ovarian Cancer ◽

Wound Healing ◽

Plant Species ◽

Human Ovarian Cancer ◽

Skov3 Cell ◽

Potential Candidate ◽

Wound Healing Assay ◽

Skov3 Cells ◽

Anti Cancer ◽

Cancer Activity

Juglone is isolated from many plant species belonging to Juglandaceae family. Recent studies have shown that Juglone exhibits various bioactivities including anti-tumor functions. However, its anti-cancer activity on human ovarian cancer SKOV3 cell has not been examined. Thus, the current study was designed to elucidate the effect of Juglone on migration of human ovarian cancer SKOV3 cells. In the present study, SKOV3 cells were incubated with Juglone at various concentrations. Wound healing assay and Transwell chambers were used to detect migration of SKOV3 treated with Juglone for 24h. The result showed that Juglone inhibited the migration of SKOV3 cells with concentration of Juglone at 25, 50 or 100μM compared with control cells. Therefore, our results indicated that Juglone may be a potential candidate of drug for ovarian cancer.

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Ghrelin enhances cisplatin sensitivity in HO-8910 PM human ovarian cancer cells

Journal of Ovarian Research ◽

10.1186/s13048-021-00907-9 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Yun Leng ◽

Can Zhao ◽

Guoliang Yan ◽

Shuangyue Xu ◽

Yinggui Yang ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Cycle Arrest ◽

Cyclin B1 ◽

Inhibitory Effect ◽

S Phase ◽

Phase Cell ◽

Ovarian Cancer Cells ◽

Cycle Arrest

Abstract Background Resistance to platinum-based chemotherapy is one of the crucial problems in ovarian cancer treatment. Ghrelin, a widely distributed peptide hormone, participates in a series of cancer progression. The aim of this study is to determine whether ghrelin influences the sensitivity of ovarian cancer to cisplatin, and to demonstrate the underlying mechanism. Methods The anti-tumor effects of ghrelin and cisplatin were evaluated with human ovarian cancer cells HO-8910 PM in vitro or in vivo. Cell apoptosis and cell cycle were analyzed via flow cytometry assay. The signaling pathway and the expression of cell cycle protein were analyzed with Western Blot. Results Our results showed that treatment with ghrelin specifically inhibited cell proliferation of HO-8910 PM and sensitized these cells to cisplatin via S phase cell cycle arrest, and enhanced the inhibitory effect of cisplatin on tumor growth of HO-8910 PM derived xenografts in vivo. Treatment with ghrelin inhibited the expression of p-Erk1/2 and p-p38, which was opposite the effect of cisplatin. However, under the treatment of ghrelin, cisplatin treatment exhibited a stronger effect on inhibiting P21 expression, upregulating p-CDK1 and cyclin B1 expression, and blocking cell cycle progression. Mechanistically, ghrelin promoted S phase cell cycle arrest and upregulated p-CDK1 and cyclin B1 expression induced by cisplatin via inhibition of p38. Conclusion This study revealed a specifically inhibitory effect of ghrelin on platinum-resistance via suppressing p-P38 and subsequently promoting p-CDK1 mediated cell cycle arrest in HO-8910 PM.

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Astaxanthin Combine with Human Serum Albumin to Abrogate Cell Proliferation, Migration, and Drug-resistant in Human Ovarian Carcinoma SKOV3 Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190225123003 ◽

2019 ◽

Vol 19 (6) ◽

pp. 792-801 ◽

Cited By ~ 7

Author(s):

Xiu-Zhen Su ◽

Ran Chen ◽

Cai-Bing Wang ◽

Xi-Lin Ouyang ◽

Yan Jiang ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Proliferation ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Phase Cell ◽

Drug Resistant ◽

Skov3 Cells ◽

Induced Apoptosis

Background: Astaxanthin (AST) shows a large range of beneficial effects together with anti-cancer and antioxidation properties. Human Serum Albumin (HSA) is the most abundant protein in blood plasma which plays the role of a depot and transport protein for many exogenous compounds. However, whether HSA could enhance AST-induced cytotoxic effects in human ovarian cancer cells has not been examined to date. Objective: This study aims to explore the anticancer effect and the molecular mechanism of AST combine with HSA induced cytotoxicity in ovarian cancer SKOV3 cells. Methods: The ovarian cancer SKOV3 cells were treated by AST combined with HSA to study the effects of cell proliferation, cell morphology, cell cycle arrest, related protein expression, nuclear transfer, cell migration, and drug-resistant. Results: Our data confirmed that AST+HSA treatment enhanced the anticancer effects of AST, arrested G1 phase cell cycle and induced apoptosis in SKOV3 cells. AST+HSA induced apoptosis via mitochondrial apoptotic pathways was related to the increased ratio of Bcl-2/Bax and activation of caspase-3. Besides, exposure of cells to AST+HSA triggered the inactivation of NF-κB and activation p53 and MAPKs signaling pathways. Furthermore, AST+HSA significantly overcome the drug-resistant and inhibited the migration of SKOV3 cells. Conclusion: AST combined treatment with HSA considerably inhibited NF-κB expression and translocation to nucleus, thereby improving the AST-induced cytotoxic effect on SKOV3 cells. These findings may provide rationale to combine AST with HSA for the treatment of ovarian cancer.

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Standardized Saponin Extract from Baiye No.1 Tea (Camellia sinensis) Flowers Induced S Phase Cell Cycle Arrest and Apoptosis via AKT-MDM2-p53 Signaling Pathway in Ovarian Cancer Cells

Molecules ◽

10.3390/molecules25153515 ◽

2020 ◽

Vol 25 (15) ◽

pp. 3515

Author(s):

Youying Tu ◽

Lianfu Chen ◽

Ning Ren ◽

Bo Li ◽

Yuanyuan Wu ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Signaling Pathway ◽

Camellia Sinensis ◽

High Purity ◽

S Phase ◽

Phase Cell ◽

P53 Signaling ◽

Cycle Arrest ◽

P53 Signaling Pathway

Ovarian cancer is considered to be one of the most serious malignant tumors in women. Natural compounds have been considered as important sources in the search for new anti-cancer agents. Saponins are characteristic components of tea (Camellia sinensis) flower and have various biological activities, including anti-tumor effects. In this study, a high purity standardized saponin extract, namely Baiye No.1 tea flower saponin (BTFS), which contained Floratheasaponin A and Floratheasaponin D, were isolated from tea (Camellia sinensis cv. Baiye 1) flowers by macroporous resin and preparative liquid chromatography. Then, the component and purity were detected by UPLC-Q-TOF/MS/MS. This high purity BTFS inhibited the proliferation of A2780/CP70 cancer cells dose-dependently, which is evidenced by the inhibition of cell viability, reduction of colony formation ability, and suppression of PCNA protein expression. Further research found BTFS induced S phase cell cycle arrest by up-regulating p21 proteins expression and down-regulating Cyclin A2, CDK2, and Cdc25A protein expression. Furthermore, BTFS caused DNA damage and activated the ATM-Chk2 signaling pathway to block cell cycle progression. Moreover, BTFS trigged both extrinsic and intrinsic apoptosis—BTFS up-regulated the expression of death receptor pathway-related proteins DR5, Fas, and FADD and increased the ratio of pro-apoptotic/anti-apoptotic proteins of the Bcl-2 family. BTFS-induced apoptosis seems to be related to the AKT-MDM2-p53 signaling pathway. In summary, our results demonstrate that BTFS has the potential to be used as a nutraceutical for the prevention and treatment of ovarian cancer.

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Role of JNK Activation and Mitochondrial Bax Translocation in Allicin-Induced Apoptosis in Human Ovarian Cancer SKOV3 Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/378684 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 19

Author(s):

Ling Xu ◽

Jin Yu ◽

Dongxia Zhai ◽

Danying Zhang ◽

Wei Shen ◽

...

Keyword(s):

Ovarian Cancer ◽

Ovarian Cancer Cell Line ◽

Biologically Active ◽

Cell Counting ◽

Human Ovarian Cancer ◽

Skov3 Cell ◽

Dependent Manner ◽

Skov3 Cells ◽

Induced Apoptosis ◽

Jnk Activation

Background. Allicin, the major component of freshly crushed garlic, is one of the most biologically active compounds of garlic; it has been reported to induce apoptosis in cancer cells; however, the mechanism by which allicin exerts its apoptotic effects is not fully understood. The aim of the present study was to further elucidate the apoptotic pathways induced by allicin in the human ovarian cancer cell line SKOV3.Methods. Cell proliferation and apoptosis were measured by cell-counting assay and flow cytometry analysis. Activation of the signaling pathway was screened by human phospho-kinase array analysis, and the activated pathway and its related proteins were further confirmed by western blot analysis.Results. Allicin induced SKOV3 cell apoptosis and JNK phosphorylation in a time- and dose-dependent manner, but these were significantly blocked by SP600125 (an inhibitor of JNK). The findings suggest that JNK phosphorylation is related to the action of allicin on SKOV3 cells. Furthermore, JNK activation induced Bcl-2 family activation, triggered mitochondria-mediated signaling pathways, and led to the translocation of a considerable amount of Bax and cytochromecrelease.Conclusions. JNK activation and mitochondrial Bax translocation are involved in allicin-induced apoptosis in SKOV3 cells. Our data input new insights to the literature of allicin-induced apoptosis.

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miR-486 Promotes the Invasion and Cell Cycle Progression of Ovarian Cancer Cells by Targeting CADM1

Analytical Cellular Pathology ◽

10.1155/2021/7407086 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Chenyang Li ◽

Yue Wang ◽

Hao Wang ◽

Bowen Wang ◽

Yunxia Wang ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Proliferation ◽

Western Blot ◽

Cell Cycle Progression ◽

Luciferase Reporter ◽

Ovarian Cancer Cells ◽

Skov3 Cell ◽

Cycle Progression ◽

Skov3 Cells

Objective. To explore the role and possible underlying mechanism of miR-486 in ovarian cancer (OC) cells. Methods. The expression of miR-486 and CADM1 was detected by qRT-PCR in OC tissues and adjacent nontumor tissues and OC cell lines. The dual-luciferase reporter gene system was used to determine the targeting relationship between miR-486 and CADM1. CCK-8, colony formation assay, Transwell, and flow cytometry were performed to detect cell proliferation, cell invasion, cell cycle progression, and the apoptotic cell death, respectively. Western blot was carried out to detect the expression of CADM1 protein and the proteins associated with cell cycle progression. Results. miR-486 was significantly upregulated in OC tissues and cells, while CADM1 expression was significantly downregulated. Dual-luciferase reporter assays further confirmed that CADM1 was a target gene of miR-486. Interference with miR-486 could inhibit the proliferation and invasion and promoted the apoptosis of SKOV3 cells. Knocking down both miR-486 and CADM1 significantly increased the SKOV3 cell proliferation, invasion, and the number of cells transitioning from the G0/G1 phase into the S phase of cell cycle and reduced the cellular apoptosis. Western blot analysis revealed that the expression of cell cycle progression-related proteins (CyclinD1, CyclinE, and CDK6) was significantly reduced, and the p21 expression was increased when interfering with both miR-486 and CADM1 expression. Conclusion. Our results suggested that miR-486 could act as a tumor promoter by targeting CADM1 and be a potential therapeutic target for the treatment of OC.

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