MicroRNA-130a is upregulated in colorectal cancer and promotes cell growth and motility by directly targeting forkhead box F2

Abstract Background Dehydrodiisoeugenol (DEH), a novel lignan component extracted from nutmeg, which is the seed of Myristica fragrans Houtt, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anticancer activity in gastrointestinal cancer remains to be investigated. Methods In this study, the anticancer effect of DEH on human colorectal cancer and its underlying mechanism were evaluated. Assays including MTT, EdU, Plate clone formation, Soft agar, Flow cytometry, Electron microscopy, Immunofluorescence and Western blotting were used in vitro. The CDX and PDX tumor xenograft models were used in vivo. Results Our findings indicated that treatment with DEH arrested the cell cycle of colorectal cancer cells at the G1/S phase, leading to significant inhibition in cell growth. Moreover, DEH induced strong cellular autophagy, which could be inhibited through autophagic inhibitors, with a rction in the DEH-induced inhibition of cell growth in colorectal cancer cells. Further analysis indicated that DEH also induced endoplasmic reticulum (ER) stress and subsequently stimulated autophagy through the activation of PERK/eIF2α and IRE1α/XBP-1 s/CHOP pathways. Knockdown of PERK or IRE1α significantly decreased DEH-induced autophagy and retrieved cell viability in cells treated with DEH. Furthermore, DEH also exhibited significant anticancer activities in the CDX- and PDX-models. Conclusions Collectively, our studies strongly suggest that DEH might be a potential anticancer agent against colorectal cancer by activating ER stress-induced inhibition of autophagy.

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Action of a library of O-glycosylation inhibitors on the growth of human colorectal cancer cells in culture

Biochemical Society Transactions ◽

10.1042/bst0330721 ◽

2005 ◽

Vol 33 (4) ◽

pp. 721-723 ◽

Cited By ~ 11

Author(s):

G. Patsos ◽

V. Hebbe-Viton ◽

R. San Martin ◽

C. Paraskeva ◽

T. Gallagher ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Growth ◽

Cancer Cells ◽

Cell Lines ◽

Growth Patterns ◽

Limited Information ◽

Human Colorectal Cancer ◽

Human Colorectal Cancer Cell ◽

Colorectal Cancer Cells ◽

Colorectal Cancer Cell Lines

O-glycosylation is thought to play a significant role in the regulation of cell growth. However, only limited information is available, and few specific and selective inhibitors have been found. We have synthesized a library of O-glycosylation inhibitors based on benzyl-O-N-acetyl-D-galactosamine. These inhibitors were tested with an established series of human colorectal cancer cell lines, which model the adenoma-carcinoma sequence. Cancer cells were incubated with the inhibitors, and examined for cell growth patterns, and cellular and subcellular glycosylation using a range of lectins with confocal microscopy. The specificity of O-glycan inhibition was confirmed for the library, relative to other forms of glycosylation. All inhibitors tested resulted in smaller cell yields. However, a differential effect on O-glycosylation was detected using the lectins showing variation of localization at a subcellular level in the various cell lines. Further differential action of the inhibitor library was observed for apoptosis and on the cell cycle with the cell lines tested. This work demonstrates that O-glycosylation is closely involved in the regulation of cell growth in colorectal cancer cells and that the generation of a library of low-molecular-mass inhibitors offers a valuable means of examining this regulation at the molecular level.

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Long noncoding RNA OCC-1 suppresses cell growth through destabilizing HuR protein in colorectal cancer

Nucleic Acids Research ◽

10.1093/nar/gky214 ◽

2018 ◽

Vol 46 (11) ◽

pp. 5809-5821 ◽

Cited By ~ 53

Author(s):

Yang Lan ◽

Xuewei Xiao ◽

Zhengchi He ◽

Yu Luo ◽

Chuanfang Wu ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Growth ◽

Long Noncoding Rna ◽

Noncoding Rna

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Targeting sphingosine kinase 2 (SphK2) by ABC294640 inhibits colorectal cancer cell growth in vitro and in vivo

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-015-0205-y ◽

2015 ◽

Vol 34 (1) ◽

Cited By ~ 34

Author(s):

Cai Xun ◽

Min-Bin Chen ◽

Li Qi ◽

Zhang Tie-Ning ◽

Xue Peng ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Growth ◽

Cancer Cell ◽

Sphingosine Kinase ◽

Colorectal Cancer Cell ◽

Cancer Cell Growth ◽

Sphingosine Kinase 2

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Down-regulation of CXCL 11 inhibits colorectal cancer cell growth and epithelial-mesenchymal transition

OncoTargets and Therapy ◽

10.2147/ott.s167872 ◽

2018 ◽

Vol Volume 11 ◽

pp. 7333-7343 ◽

Cited By ~ 13

Author(s):

Yu Jie Gao ◽

De Lin Liu ◽

Sheng Li ◽

Gao Feng Yuan ◽

Li Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Growth ◽

Cancer Cell ◽

Epithelial Mesenchymal Transition ◽

Colorectal Cancer Cell ◽

Cancer Cell Growth ◽

Down Regulation ◽

Mesenchymal Transition

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The ERK pathway involves positive and negative regulations of HT-29 colorectal cancer cell growth by extracellular zinc

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00047.2003 ◽

2003 ◽

Vol 285 (6) ◽

pp. G1181-G1188 ◽

Cited By ~ 19

Author(s):

Ki-Sook Park ◽

Nam-Gu Lee ◽

Ki-Hoo Lee ◽

Jeong Taeg Seo ◽

Kang-Yell Choi

Keyword(s):

Colorectal Cancer ◽

Signal Transduction ◽

Cell Proliferation ◽

Cell Growth ◽

Cyclin D1 ◽

Growth Regulation ◽

Erk Pathway ◽

Differential Growth ◽

Erk Activation ◽

Ht 29

Dietary zinc is an important trace element in the body and is related to both cell proliferation and growth arrest. A recent study found that extracellular zinc-sensing receptors trigger intracellular signal transduction in HT-29 human colorectal cancer cells. However, the signaling mechanism causing this growth regulation by extracellular zinc is not clearly understood. At 10- and 100-μM levels of ZnCl2 treatment, HT-29 cell growth and proliferation increased and decreased, respectively, in a minimally serum-starved medium (MSSM). A lack of significant increase in intracellular zinc levels after zinc treatment suggested that this differential growth regulation of HT-29 cells by extracellular zinc is acquired by receptor-mediated signal transduction. Moreover, this zinc-induced growth regulation was differentially affected by PD-98059, suggesting the involvement of the ERK pathway. Transient ERK activation and subsequent cyclin D1 induction were observed on adding 10 μM ZnCl2 in MSSM in the presence of cell proliferation. On the other hand, prolonged ERK activity was observed with a subsequent increase of cyclin D1 and p21Cip/WAF1 on adding 100 μM ZnCl2 in MSSM, and this was associated with nonproliferation. Moreover, this ERK activation and cyclin D1 and p21Cip/WAF1 induction were abolished by PD-98059 pretreatment. The differential regulations of cell growth, ERK activities, and cyclin D1 and p21Cip/WAF1 inductions were also observed in serum-enriched medium containing higher zinc concentrations. Therefore, differential cell cycle regulator induction occurs by a common ERK pathway in the differential growth regulation of HT-29 cells by extracellular zinc.

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