Valproate inhibits colon cancer growth through cell cycle modification in vivo and in vitro

Strey, Christoph W.; Schamell, Lea; Oppermann, Elsie; Haferkamp, Axel; Bechstein, Wolf O.; Blaheta, Roman A.

doi:10.3892/etm.2011.202

Cited by 9 publications

(14 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell-cycle progression is regulated by a series of checkpoint proteins. Elevated expressions of cyclin D1, cyclin E, and c-Myc have been reported in colon cancer [20]. Modification of the cell cycle has been considered as an important therapeutic strategy for colon cancer treatment [20].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Long non-coding XIAP-AS1 regulates cell proliferation, invasion and cell cycle in colon cancer

Lü

Sheng

2019

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

Colon cancer is one of the most commonly diagnosed and deadly cancers worldwide. Further understanding of the biological mechanisms is important for exploring the molecular biomarkers and therapeutic targets of this disease. Dysregulation of long non-coding RNAs (lncRNAs) has been reported to be associated with the development and progression of various cancers. XIAP-AS1 is a novel lncRNA, which can regulate apoptosis in gastric cancer cells. However, the role of XIAP-AS1 in colorectal cancer (CRC) remains unclear. In this study, we found that XIAP-AS1 expression was significantly increased in CRC tissues and its expression showed a positive correlation with TNM stage and cumulative survival rate of CRC. To investigate whether XIAP-AS1 regulates the progression of CRC, we knocked down its expression in several CRC cell lines. CCK-8 assays showed that XIAP-AS1 knockdown remarkably suppressed CRC cell growth and arrested the cell cycle at the G0/G1 phase (flow cytometric analysis). Furthermore, XIAP-AS1 knockdown also remarkably blocked cell invasion of colon cancer cells by regulating the expression of EMT markers, such as E-cadherin, ZO-1, vimentin, and N-cadherin. Importantly, we found that XIAP-AS1 knockdown significantly reduced STAT3 phosphorylation. Overall, this study suggests that lncRNA XIAP-AS1 might serve as a potential oncogene for colon cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Long non-coding XIAP-AS1 regulates cell proliferation, invasion and cell cycle in colon cancer

Lü

Sheng

2019

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

show abstract

“…Several studies have evaluated GSK3 as a potential therapeutic target for cancer treatment, such as in prostate cancer (43), melanoma (30), glioblastoma (44), pancreatic cancer (45), and colorectal cancer (46). Some studies have also evaluated the therapeutic effect of VPA on colorectal cancer (47,48) through inhibiting the enhanced histone deacetylase activity; however, such studies did not refer to its effect as a GSK3 inhibitor. None of these previous reports suggested the potential of GSK3 inhibition as a CSC-targeting therapy.…”

Section: Discussionmentioning

confidence: 99%

The Tissue-Reconstructing Ability of Colon CSCs Is Enhanced by FK506 and Suppressed by GSK3 Inhibition

Ishida

Koyanagi-Aoi

Oshima

et al. 2017

Molecular Cancer Research

View full text Add to dashboard Cite

Cancer stem cells (CSC) are capable of reconstructing cancer tissues, are involved in both recurrence and metastasis, and contribute to therapeutic resistance. Therefore, elucidating the molecular mechanism in CSCs is important to successfully treat unresectable cancers. Previously, we observed that colon cancer stem-like cells can be induced from human colon cancer cell lines by retrovirally introducing OCT3/4, SOX2, and KLF4, and we have designated such cells as induced cancer stem cells (iCSC). In the current study, we used iCSCs to evaluate the molecular mechanism of colon CSCs and developed new methods to control them. The spheres that were derived in vitro from the iCSCs, but not those from parental cells, mimicked human colon cancer tissues in terms of their immunohistologic patterns; therefore, sphere-forming ability was assessed as a measure of the tissuereconstructing ability of iCSCs. Interestingly, the calcineurin inhibitor FK506 enhanced the sphere-forming ability of iCSCs, whereas GSK3 inhibition by RNAi, CHIR99021, and valproic acid (VPA) impeded the sphere-forming ability and expansion of iCSCs. FK506 and GSK3 inhibition showed the opposite effect regarding the NFATc3 localization of iCSCs. These data reveal the crucial role that NFAT localization, as regulated by calcineurin and GSK3, plays in the tissue-reconstructing ability of colon cancer stem cells and the potential of GSK3 inhibitors, such as VPA, in colon cancer stem cell-targeting therapy.

show abstract

“…valproic acid, estradiol, and gefitinib) by querying CMap to restore the normal expression of five targets. Notably, the valproic acid not only inhibits CRC cells growth through cell cycle modification but also has the ability to reverse aberrant DNA methylation partially (Strey et al, 2011;Brodie and Brandes, 2014;Bressy et al, 2017). Moreover, estradiol has been found that it reduced proliferation and apoptosis in CRC (Sasso et al, 2019).…”

Section: Design Of Multiple-molecule Drugs For Preventing the Progresmentioning

confidence: 99%

Investigation of the Genome-Wide Genetic and Epigenetic Networks for Drug Discovery Based on Systems Biology Approaches in Colorectal Cancer

Yeh

Chen

2020

Front. Genet.

View full text Add to dashboard Cite

Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide. The mechanisms leading to the progression of CRC are involved in both genetic and epigenetic regulations. In this study, we applied systems biology methods to identify potential biomarkers and conduct drug discovery in a computational approach. Using big database mining, we constructed a candidate protein-protein interaction network and a candidate gene regulatory network, combining them into a genome-wide genetic and epigenetic network (GWGEN). With the assistance of system identification and model selection approaches, we obtain real GWGENs for early-stage, mid-stage, and late-stage CRC. Subsequently, we extracted core GWGENs for each stage of CRC from their real GWGENs through a principal network projection method, and projected them to the Kyoto Encyclopedia of Genes and Genomes pathways for further analysis. Finally, we compared these core pathways resulting in different molecular mechanisms in each stage of CRC and identified carcinogenic biomarkers for the design of multiple-molecule drugs to prevent the progression of CRC. Based on the identified gene expression signatures, we suggested potential compounds combined with known CRC drugs to prevent the progression of CRC with querying Connectivity Map (CMap).

show abstract

Valproate inhibits colon cancer growth through cell cycle modification in vivo and in vitro

Cited by 9 publications

References 32 publications

RETRACTED ARTICLE: Long non-coding XIAP-AS1 regulates cell proliferation, invasion and cell cycle in colon cancer

RETRACTED ARTICLE: Long non-coding XIAP-AS1 regulates cell proliferation, invasion and cell cycle in colon cancer

The Tissue-Reconstructing Ability of Colon CSCs Is Enhanced by FK506 and Suppressed by GSK3 Inhibition

Investigation of the Genome-Wide Genetic and Epigenetic Networks for Drug Discovery Based on Systems Biology Approaches in Colorectal Cancer

Contact Info

Product

Resources

About