scholarly journals Rosmarinic Acid Methyl Ester Regulates Ovarian Cancer Cell Migration and Reverses Cisplatin Resistance by Inhibiting the Expression of Forkhead Box M1

2020 ◽  
Vol 13 (10) ◽  
pp. 302
Author(s):  
Soo Hyun Lim ◽  
Ki Hong Nam ◽  
Kyungtae Kim ◽  
Sang Ah Yi ◽  
Jaecheol Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Methyl Ester ◽  
Cancer Cells ◽  
Rosmarinic Acid ◽  
Target Genes ◽  
Acid Methyl Ester ◽  
Ovarian Cancer Cells ◽  
Forkhead Box ◽  
Acid Methyl ◽  
Forkhead Box M1

Rosmarinic acid methyl ester (RAME), a derivative of rosmarinic acid (RA), is reported to have several therapeutic effects, including anti-tumor effects against cervical cancer. However, its anti-tumor effects in ovarian cancer is unclear. In this study, we studied the molecular pathways associated with the anti-tumor effects of RAME in ovarian cancer. To identify the effects of RAME in ovarian cancer, RNA sequencing was performed in RAME-treated ovarian cancer cells; we found that RAME treatment downregulated the genes closely involved with the target genes of the transcription factor Forkhead box M1 (FOXM1). It was reported that FOXM1 is overexpressed in a variety of cancer cells and is associated with cell proliferation and tumorigenesis. Therefore, we hypothesized that FOXM1 is a key target of RAME; this could result in its anti-tumor effects. Treatment of ovarian cancer cells with RAME-inhibited cell migration and invasion, as shown by wound healing and transwell migration assays. To examine whether RAME represses the action of FOXM1, we performed quantitative RT-PCR and ChIP-qPCR. Treatment of ovarian cancer cells with RAME decreased the mRNA expression of FOXM1 target genes and the binding of FOXM1 to its target genes. Moreover, FOXM1 expression was increased in cisplatin-resistant ovarian cancer cells, and combination treatment with RAME and cisplatin sensitized the cisplatin-resistant ovarian cancer cells, which was likely due to FOXM1 inhibition. Our research suggests that RAME is a promising option in treating ovarian cancer patients, as it revealed a novel molecular pathway underlying its anti-tumor effects.

scholarly journals Forkhead Box Protein C2 Promotes Epithelial-Mesenchymal Transition, Migration and Invasion in Cisplatin-Resistant Human Ovarian Cancer Cell Line (SKOV3/CDDP)

2016 ◽  
Vol 39 (3) ◽  
pp. 1098-1110 ◽  
Author(s):  
Chanjuan Li ◽  
Hongjuan Ding ◽  
Jing Tian ◽  
Lili Wu ◽  
Yun Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Epithelial Mesenchymal Transition ◽  
Ovarian Cancer Cell Line ◽  
Cancer Cell Line ◽  
Ovarian Cancer Cells ◽  
Skov3 Cell ◽  
Mesenchymal Transition ◽  
Forkhead Box

Background/Aims: Forkhead Box Protein C2 (FOXC2) has been reported to be overexpressed in a variety of human cancers. However, it is unclear whether FOXC2 regulates epithelial-mesenchymal transition (EMT) in CDDP-resistant ovarian cancer cells. The aim of this study is to investigate the effects of FOXC2 on EMT and invasive characteristics of CDDP-resistant ovarian cancer cells and the underlying molecular mechanism. Methods: MTT, Western blot, scratch wound healing, matrigel transwell invasion, attachment and detachment assays were performed to detect half maximal inhibitory concentration (IC50) of CDDP, expression of EMT-related proteins and invasive characteristics in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) and its parental cell line (SKOV3). Small hairpin RNA (shRNA) was used to knockdown FOXC2 and analyze the effect of FOXC2 knockdown on EMT and invasive characteristics of SKOV3/CDDP cells. Also, the effect of FOXC2 upregulation on EMT and invasive characteristics of SKOV3 cells was analyzed. Furthermore, the molecular mechanism underlying FOXC2-regulating EMT in ovarian cancer cells was determined. Results: Compared with parental SKOV3 cell line, SKOV3/CDDP showed higher IC50 of CDDP (43.26μM) (P<0.01) and acquired EMT phenotype and invasive characteristics. Gain- and loss-of-function assays indicated that shRNA-mediated FOXC2 knockdown could reverse EMT and reduce the capacity of migration, invasion, attachment and detachment in SKOV3/CDDP cell line and upregulation of FOXC2 could induce the reverse effects in parental SKOV3 cell line. Furthermore, it was found that activation of ERK or AKT/GSK-3β signaling pathways was involved in FOXC2-promoting EMT in CDDP-resistant ovarian cancer cells. Conclusions: Taken together, these data demonstrate that FOXC2 may be a promoter of EMT phenotype in CDDP-resistant ovarian cancer cells and a potential therapeutic target for the treatment of advanced ovarian cancer.

scholarly journals MicroRNA-338-3p suppresses ovarian cancer cells growth and metastasis: implication of Wnt/catenin beta and MEK/ERK signaling pathways

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Ruitao Zhang ◽  
Huirong Shi ◽  
Fang Ren ◽  
Wei Feng ◽  
Yuan Cao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Target Genes ◽  
Erk Signaling ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Inhibition Of Proliferation ◽  
Mesenchymal Transition ◽  
Biomedical Databases

Abstract Background Downregulation of microRNA-338-3p (miR-338-3p) was detected in many malignant tumors, which indicated miR-338-3p might serve as a role of antioncogene in those cancers. The present study aimed to explore the roles of miR-338-3p in the growth and metastasis of ovarian cancer cells and elaborate the underlying possible molecular mechanism. Methods Multiply biomedical databases query and KEGG pathway enrichment assay were used to infilter possible target genes and downstream pathways regulated by miR-338-3p. Overexpression miR-338-3p lentiviral vectors were transfected into ovarian cancer OVCAR-3 and OVCAR-8 cells, cell proliferation, migration and invasion were analyzed by MTT, colony formation, transwell, Matrigel assay and xenograft mouse model. One 3′-untranslated regions (UTRs) binding target gene of miR-338-3p, MACC1 (MET transcriptional regulator MACC1), and its regulated gene MET and downstream signaling pathway activities were examined by western blot. Results Biomedical databases query indicated that miR-338-3p could target MACC1 gene and regulate Met, downstream Wnt/Catenin beta and MEK/ERK pathways. Rescue of miR-338-3p could inhibit the proliferation, migration and invasion of ovarian cancer cells, and suppress the growth and metastasis of xenograft tumor. Restoration of miR-338-3p could attenuate MACC1 and Met overexpression induced growth, epithelial to mesenchymal transition (EMT) and activities of Wnt/Catenin beta and MEK/ERK signaling in vitro and in vivo. Conclusions The present data indicated that restoration of miR-338-3p could suppress the growth and metastasis of ovarian cancer cells, which might due to the inhibition of proliferation and EMT induced by MACC1, Met and its downstream Wnt/Catenin beta and MEK/ERK signaling pathways.

scholarly journals Upregulation of forkhead box O3 transcription is involved in C2-ceramide induced apoptosis and autophagy in ovarian cancer cells in vitro

2014 ◽  
Vol 10 (6) ◽  
pp. 3099-3105 ◽  
Author(s):  
ZHISHAN JIN ◽  
LANG ZHENG ◽  
XIAOYAN XIN ◽  
YUANYUE LI ◽  
TENG HUA ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Forkhead Box ◽  
Induced Apoptosis

scholarly journals Metformin Affects the Transcriptomic Profile of Chicken Ovarian Cancer Cells

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 30
Author(s):  
Lalitha Gopalan ◽  
Aswathy Sebastian ◽  
Craig A. Praul ◽  
Istvan Albert ◽  
Ramesh Ramachandran
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Pathway Analysis ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Ovarian Cancer Cells ◽  
Metformin Treatment ◽  
Mesenchymal Transition ◽  
Sphere Formation ◽  
Upstream Regulators

Ovarian cancer is the most lethal gynecological malignancy in women. Metformin intake is associated with a reduced incidence of ovarian cancer and increased overall survival rate. We determined the effect of metformin on sphere formation, extracellular matrix invasion, and transcriptome profile of ovarian cancer cells (COVCAR) isolated from ascites of chickens that naturally developed ovarian cancer. We found that metformin treatment significantly decreased sphere formation and invasiveness of COVCAR cells. RNA-Seq data analysis revealed 0, 4, 365 differentially expressed genes in cells treated with 0.5, 1, 2 mM metformin, respectively compared to controls. Transcriptomic and ingenuity pathway analysis (IPA) revealed significant downregulation of MMP7, AICDA, GDPD2, APOC3, APOA1 and predicted inhibition of upstream regulators NFKB, STAT3, TP53 that are involved in epithelial–mesenchymal transition, DNA repair, and lipid metabolism. The analysis revealed significant upregulation of RASD2, IHH, CRABP-1 and predicted activation of upstream regulators VEGF and E2F1 that are associated with angiogenesis and cell cycle. Causal network analysis revealed novel pathways suggesting predicted inhibition of ovarian cancer through master regulator ASCL1 and dataset genes DCX, SEMA6B, HEY2, and KCNIP2. In summary, advanced pathway analysis in IPA revealed novel target genes, upstream regulators, and pathways affected by metformin treatment of COVCAR cells.

scholarly journals Newly synthesized 3-(4-chloro-phenyl)-3-hydroxy-2,2-dimethyl-propionic acid methyl ester derivatives selectively inhibit the proliferation of colon cancer cells

RSC Advances ◽  
2020 ◽  
Vol 10 (15) ◽  
pp. 8825-8841
Author(s):  
Samir M. El Rayes ◽  
Ahmed Aboelmagd ◽  
Mohamed S. Gomaa ◽  
Walid Fathalla ◽  
Ibrahim A. I. Ali ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Methyl Ester ◽  
Cancer Cells ◽  
Propionic Acid ◽  
Acid Methyl Ester ◽  
Colon Cancer Cells ◽  
Structure Modification ◽  
Acid Methyl

A series of 24 compounds were synthesized based on structure modification of the model methyl-3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropanoate as potent HDACIs.

scholarly journals Identification of a novel S6K1 inhibitor, rosmarinic acid methyl ester, for treating cisplatin-resistant cervical cancer

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ki Hong Nam ◽  
Sang Ah Yi ◽  
Gibeom Nam ◽  
Jae Sung Noh ◽  
Jong Woo Park ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Methyl Ester ◽  
Rosmarinic Acid ◽  
Acid Methyl Ester ◽  
Acid Methyl

scholarly journals Triterpenoids and Alkaloids from the Roots of Peganum Nigellastrum

2008 ◽  
Vol 3 (2) ◽  
pp. 1934578X0800300
Author(s):  
Zhongze Ma ◽  
Yoshio Hano ◽  
Feng Qiu ◽  
Gang Shao ◽  
Yingjie Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Methyl Ester ◽  
Cancer Cells ◽  
Acid Methyl Ester ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Pentacyclic Triterpenoids ◽  
Acid Methyl ◽  
Androgen Independent ◽  
Chemical Evidence

Four lupane-type triterpenoids (1–4) and seven alkaloids (5–11) were isolated from the roots of Peganum nigellastrum. On the basis of spectroscopic and chemical evidence, the structures of the compounds were elucidated as 3α-hydroxy-27- trans-caffeoyloxylup-20(29)-en-28-oic acid methyl ester (1), 3β-hydroxy-27- trans-caffeoyloxylup-20(29)-en-28-oic acid methyl ester (2), 3α-acetoxy-27- trans-caffeoyloxylup-20(29)-en-28-oic acid methyl ester (3), 3β-acetoxy-27- trans-caffeoyloxylup-20(29)-en-28-oic acid methyl ester (4), luotonin C (5), luotonin D (6), harmine (7), harmol (8), harmaline (9), deoxyvasicinone (10) and vasicinone (11). Compounds 1, 3 and 4 are novel triterpenoids, and these pentacyclic triterpenoids were evaluated for their cytotoxicity against the androgen-sensitive LNCaP and androgen-independent PC-3 human prostate cancer cells.

scholarly journals MiRNA-802 suppresses proliferation and migration of epithelial ovarian cancer cells by targeting YWHAZ

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Bo Yang ◽  
Li Sun ◽  
Lei Liang
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Target Genes ◽  
Gene Prediction ◽  
Biological Effects ◽  
Expression Level ◽  
Ovarian Cancer Cells ◽  
And Migration

Abstract Background The imbalance of expression of microRNA-802 may have a significant place in tumor progression. However, the bio-function of epithelial ovarian cancer cells remains unclear. Therefore, we setup this study to explore the pathogenesis of epithelial ovarian cancer based on microRNA-802. Methods RT-qPCR analysis was used to measure the expression level of microRNA802 and YWHAZ in epithelial ovarian cancer. CCK-8, colony formation, flow cytometry and transwell assay were used to detect the effects of microRNA-802 on cell proliferation, apoptosis, invasion and migration. Target gene prediction and screening, luciferase reporting experiments were applied to validate the downstream target genes of microRNA-802. The effects of microRNA-802 on the expression of YWHAZ and its biological effects were measured by Western blotting and RT-qPCR. Results Compared with normal cell lines and tissues, the expression level of microRNA-802 was obviously down-regulated in cancer related cell lines and tissues. Overexpression of microRNA-802 could obviously inhibit the invasion and proliferation and induce apoptosis. In addition, YWHAZ was the binding target protein of miR-802 for epithelial ovarian cancer cells. YWHAZ was obviously up-regulated in human epithelial ovarian cancer cells, and YWHAZ was negatively correlated with the expression of miR-802. YWHAZ can partly eliminate the inhibitory effect caused by overexpression of miR-802 on growth and metastasis of epithelial ovarian cancer cells. Conclusion miR-802 can regulate the occurrence and development of epithelial ovarian cancer by targeting YWHAZ.

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