scholarly journals A Newly Identified lncBCAS1-4_1 Associated With Vitamin D Signaling and EMT in Ovarian Cancer Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Yaqi Xue ◽  
Ping Wang ◽  
Fei Jiang ◽  
Jing Yu ◽  
Hongmei Ding ◽  
...  

Long noncoding RNAs (lncRNAs) were identified rapidly due to their important role in many biological processes and human diseases including cancer. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] and its analogues are widely applied as preventative and therapeutic anticancer agents. However, the expression profile of lncRNAs regulated by 1α,25(OH)2D3 in ovarian cancer remains to be clarified. In the present study, we found 606 lncRNAs and 102 mRNAs that showed differential expression (DE) based on microarray data. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the DE genes were mainly enriched in TGF-β, MAPK, Ras, PI3K-Akt, and Hippo signaling pathways, as well as the vitamin D-related pathway. We further assessed the potential lncRNAs that linked vitamin D signaling with EMT, and lncBCAS1-4_1 was identified in the first time. Moreover, we found that the most upregulated lncBCAS1-4_1 showed 75% same transcripts with CYP24A1 (metabolic enzyme of 1α,25(OH)2D3). Finally, the lncBCAS1-4_1 gain-of-function cell model was established, which demonstrated that the knockdown of lncBCAS1-4_1 inhibited the proliferation and migration of ovarian cancer cells. Furthermore, lncBCAS1-4_1 could resist the antitumor effect of 1α,25(OH)2D3, which was associated with upregulated ZEB1. These data provide new evidences that lncRNAs served as a target for the antitumor effect of 1α,25(OH)2D3.

2010 ◽  
pp. P1-9-P1-9
Author(s):  
J Tang ◽  
P Li ◽  
AKW Tse ◽  
SV Nicosia ◽  
X Zhang ◽  
...  

2021 ◽  
Author(s):  
Xiaodi Li ◽  
Yanwen Fang ◽  
Zhicai Fang ◽  
Ping Wang ◽  
Jun Zhu

Abstract To estimate the effect of a steady-state magnetic field (SMF) with low magnetic intensity gradient on the apoptosis-promoting factors related to cancer cells, we systematically select SMF with 0.2T, 0.4T and 0.6T to study their effect on different ovarian cancer lines. An in vitro cell model system about two kinds of ovarian cancer lines is established, whose viability and intracellular factors are detected by CCK-8, confocal microscopy and flow cytometry method. The results demonstrate that the apoptosis rate of ovarian cancer cells is increased with the enhancement of SMF magnetic intensity. Furthermore, we detect an increasing ROS and intracellular Ca2+ levels in ovarian cancer cells, which can be caused by SMF. The results suggest that ROS and Ca2+ levels are the main reason for the significant apoptosis of ovarian cancer cell lines in SMF. Moreover, an in vivo experiment also reveals that SMF has a strong inhibitory effect on ovarian cancer. Therefore, the inhibitory strategy is an effective, which has a great potential in the treatment of drug-resistant ovarian cancer.


Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2493
Author(s):  
Jerneja Kladnik ◽  
James P. C. Coverdale ◽  
Jakob Kljun ◽  
Hilke Burmeister ◽  
Petra Lippman ◽  
...  

Drug resistance to existing anticancer agents is a growing clinical concern, with many first line treatments showing poor efficacy in treatment plans of some cancers. Resistance to platinum agents, such as cisplatin, is particularly prevalent in the treatment of ovarian cancer, one of the most common cancers amongst women in the developing world. Therefore, there is an urgent need to develop next generation of anticancer agents which can overcome resistance to existing therapies. We report a new series of organoruthenium(II) complexes bearing structurally modified pyrithione ligands with extended aromatic scaffold, which overcome platinum and adriamycin resistance in human ovarian cancer cells. The mechanism of action of such complexes appears to be unique from that of cisplatin, involving G1 cell cycle arrest without generation of cellular ROS, as is typically associated with similar ruthenium complexes. The complexes inhibit the enzyme thioredoxin reductase (TrxR) in a model system and reduce cell motility towards wound healing. Importantly, this work highlights further development in our understanding of the multi-targeting mechanism of action exhibited by transition metal complexes.


2021 ◽  
Author(s):  
Pegah Varamini ◽  
Kimmi Dhiman ◽  
Sepideh Khazeni ◽  
Frieda Mansfeld ◽  
Istvan Toth

Abstract Gonadotropin-releasing hormone (GnRH) analogs (e.g., triptorelin) are developed to treat hormone-dependent reproductive cancers. However, these analogs lack any significant direct antitumor activity to make them suitable for hormone-refractory reproductive cancers. In this study, we modified GnRH peptide and triptorelin to improve their stability, pharmacokinetic properties, and potency and subsequently broaden their clinical applications in cancer. We investigated biological properties of lipid-modified GnRH analogs, with/without D-amino acid substitution at position 6 to yield GnRH- and triptorelin-based derivatives, respectively, in prostate and ovarian cancer cells. We showed that the improved stability due to lipid-modification and D-amino acid substitution played a pivotal role in enhancing GnRH receptor-mediated direct antiproliferative activity (up to 4.5-fold higher than triptorelin) and gonadotropin-releasing potency. Furthermore, sex steroids played significant but contrasting roles in regulating the direct antiproliferative activity of the lipopeptides in cancer cells. The superior activity of these GnRH analogs over triptorelin renders promises for developing new GnRH receptor ligands to treat hormone-dependent and -refractory cancers, as well as emerging new targeting moieties for the delivery of anticancer agents in GnRH receptor-overexpressing cancers.


2020 ◽  
Vol 19 (18) ◽  
pp. 2211-2222 ◽  
Author(s):  
Kikoleho Richa ◽  
Rituparna Karmaker ◽  
Naruti Longkumer ◽  
Vishal Das ◽  
Pulak J. Bhuyan ◽  
...  

Background: Isothiocyanates (ITCs) are small molecules that are important in synthetic organic chemistry, but their actual importance lies in their potential as anti-carcinogens. Through this piece of work, an effort was made to assess the anti-cancer activity of some simple ITCs which can be synthesized through easy greener pathways. Methods: Cell proliferation assay was performed on ovarian cancer cells (PA-1) and non-tumorigenic ovarian epithelial cells (IOSE-364). Furthermore, qRT-PCR for transcript expression levels of Spindlin1 and caspases in ovarian cancer cells and cell cycle analysis was performed. In silico studies were incorporated to understand the mode of ligand-protein interaction, ADME/Toxicity and drug-likeliness parameters. Density functional theory studies have been also been employed on the ITCs to assess their efficiency in anticancer activity. Results: An inexpensive, environmentally benign pathway has been developed for synthesizing a series of ITCs. Among the synthesized ITCs, NC6 showed better cytotoxic effects as compared to its counterparts. Novel findings revealed that NC6 had 5-folds lower transcript expression levels of Spindlin1 and induced caspases 3 and 7 expressions assessed by qRT-PCR in ovarian cancer cells. Furthermore, flow cytometry assay showed the cell cycle arrest at G1/S phase of cell cycle. The molecular docking studies revealed favorable binding affinities and the physiochemical parameters were predicted to be compatible with drug-likeliness. Conclusion: The results demonstrated the possibility that small isothiocyanate molecules which can be synthesized by a simple green methodology, can pose as promising candidates for their application as anticancer agents.


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