Laminin 521 Modulates the Сytotoxic Effect of 5-Fluorouracil on Colorectal Cancer HT29 Cells

2019 ◽  
Vol 35 (6) ◽  
pp. 73-79
Author(s):  
A. Turchinovich ◽  
I.M. Tsypina ◽  
V.G. Zgoda ◽  
S.V. Nikulin ◽  
D.V. Maltseva

The cytotoxic effect of 5-fluorouracil (5FU) and regorafenib (RF)-drugs with different mechanisms of action used to treat colorectal cancer-on the HT29 cell line when cultured on plastic and laminin 521 (LM-521) has been studied. It was shown for the first time that LM-521 can increase the sensitivity of tumor cells to 5FU. Based on the analysis of the transcriptome and proteome, a possible mechanism of the observed effect of LM-521 on HT29 cell viability was proposed. The interaction of β1-containing integrins on the cell surface with LM-521 can activate the FAK/PI3K/Akt signaling pathways, promote phosphorylation of the YAP transcription coactivator and its binding to a complex with the 14-3-3σ protein. The formation of such complex leads to the YAP retention in the cytoplasm, prevents its transport to the nucleus and the activation of anti-apoptotic gene transcription. apoptosis, β1 integrin, colorectal cancer, laminin 521 (laminin-11), regorafenib, 5-fluorouracil, HT29, ITGB1, LAMA5, YAP, SFN, 14-3-3σ The study was funded by the Russian Science Foundation (Project 17-14-01338).

2016 ◽  
Vol 11 (5) ◽  
pp. 1934578X1601100 ◽  
Author(s):  
Leina El Hosry ◽  
Laurent Boyer ◽  
Elnur E. Garayev ◽  
Fathi Mabrouki ◽  
Sok-Siya Bun ◽  
...  

Fourteen compounds belonging to different chemical classes were characterized in the roots and fruits extracts from Berberis libanotica, using the same HPLC-DAD-MS method. Thirteen were reported, for the first time, from the fruits whereas the roots contained mostly alkaloids of which 3 out of 5 are reported for the first time. Their structures were established on the basis of MS data as gallic acid (1), chlorogenic acid (2), delphinidin (3), oxyacanthine (4), rutin (5), hyperoside (6), berbamine (7), isoquercitrin (8), quercitrin (9), jatrorrhizine (10), palmatine (11), berberine (12), quercetin (13) and luteolin (14). Extracts containing compounds 4 and 7 showed significant cytotoxicity against the HT29 cell line with an IC50 of 12.2–26.1 μg/mL. Fruits extracts, due mostly to compounds 1 and 2, showed potent antioxidant activities with an EC50 of 0.0025-0.019 mg/mL.


2020 ◽  
Vol 65 ◽  
pp. 104756 ◽  
Author(s):  
Pooneh Movahedi Shad ◽  
Shohreh Zare Karizi ◽  
Raheleh Safaie Javan ◽  
Amir Mirzaie ◽  
Hassan Noorbazargan ◽  
...  

2020 ◽  
Vol 26 (4) ◽  
pp. 364-381
Author(s):  
Mina Yavari ◽  
◽  
Changiz Ahmadizadeh ◽  

Aims: Defensins are cysteine-rich antimicrobial cationic peptides and BAX is a proapoptotic gene that can cause cell death. This study aimed to investigate the effect of cellular extract of co-cultured Lactobacillus casei on the expression of BAX and human β-defensin 2 (hBD-2) genes in HT29 cells. Methods & Materials: This experimental study was conducted in the Research Center for Pharmaceutical Nanotechnology of Tabriz University of Medical Sciences in 2017. The HT29 cell line was obtained from the Pasteur Institute of Iran, and cells were assessed using Microculture Tetrazolium Test (MTT) after culturing. DNA was extracted from the treated cells, and then the DNA ladder assay was carried out. After preparing cDNA, the expression levels of BAX and hBD-2 genes in the HT29 cell line were measured using a real-time Polymerase Chain Reaction (PCR) method. Findings: The results of the MTT assay indicated that Lactobacillus casei inhibited the proliferation of HT29 cells and induced apoptosis in these cells. Results of DAPI staining and DNA ladder assay obtained from treating HT29 cells by Lactobacillus casei showed qualitative changes in cell apoptosis. Moreover, realtime PCR results indicated that Lactobacillus casei bacteria significantly increased the expression of the hBD-2 gene in HT29 colon cancer cells within 12-24 hours (P= 0.023), while BAX gene expression showed no significant change in the first 24 hours (P= 0.37). Conclusion: The extract of Lactobacillus casei can be used to stimulate cancer cells to produce β-defensins, inhibit pathogens, prevent the stimulation of cellular signaling, and fight antibiotic-resistant bacteria.


2019 ◽  
Vol 35 (5) ◽  
pp. 29-35 ◽  
Author(s):  
M.R Raigorodskaya ◽  
G.A. Belyakova ◽  
A. Turchinovich

The expression of the LAMA5 gene encoding the laminin α5 chain has been inhibited in the line HT29 cells. The treatment with 5-fluorouracil (5FU) and regorafenib (RF) showed that the knockdown of LAMA5 increases the sensitivity of the HT29 cells to 5FU by 2.2 times and does not affect their sensitivity to RF. The data of transcriptome analysis indicate that the observed changes in the sensitivity to 5FU may be caused by an activation of signaling pathways of the endoplasmic reticulum stress in the HT29 cells. In the case of RF, this effect can be compensated by a 2-fold decrease in the expression of the main RF transporter in HT29 cells. apoptosis, colorectal cancer, laminins, drag resistance, knockdown, regorafenib, endoplasmic reticulum stress, 5-fluorouracil, laminin α5 chain, endogenous expression, HT29, LAMA5, UPR. The study was supported by the Russian Science Foundation (Project 17-14-01338).


Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3714 ◽  
Author(s):  
Natalia Calonghi ◽  
Carla Boga ◽  
Dario Telese ◽  
Silvia Bordoni ◽  
Giorgio Sartor ◽  
...  

9-Hydroxystearic acid (9-HSA) is an endogenous cellular lipid that possesses antiproliferative and selective effects against cancer cells. A series of derivatives were synthesized in order to investigate the effect of the substituent in position 9 and on the methyl ester functionality on the biological activity. The two separate enantiomers of methyl 9-hydroxystearate and of methyl 9-aminostearate showed antiproliferative activity against the HT29 cell line. This indicates the importance of position 9 groups being able to make hydrogen bonding with the molecular target. Further, this effect must be preserved when the carboxy group of 9-HSA is esterified. The biological tests showed that the amines, contrarily to methyl esters, resulted in cytotoxicity. A deep investigation on the effect of methyl (R)-9-hydroxystearate on HT29 cells showed an antiproliferative effect acting through the CDKN1A and MYCBP gene expression.


Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2968 ◽  
Author(s):  
Yi Yang ◽  
Suresh Bhosle ◽  
Young Yu ◽  
So-Yeon Park ◽  
Rui Zhou ◽  
...  

Lichens produce various unique chemicals that are used in the pharmaceutical industry. To screen for novel lichen secondary metabolites that inhibit the stemness potential of colorectal cancer cells, we tested acetone extracts of 11 lichen samples collected in Chile. Tumidulin, isolated from Niebla sp., reduced spheroid formation in CSC221, DLD1, and HT29 cells. In addition, mRNA expressions and protein levels of cancer stem markers aldehyde dehydrogenase-1 (ALDH1), cluster of differentiation 133 (CD133), CD44, Lgr5, and Musashi-1 were reduced after tumidulin treatment. Tumidulin decreased the transcriptional activity of the glioma-associated oncogene homolog zinc finger protein (Gli) promoter in reporter assays, and western blotting confirmed decreased Gli1, Gli2, and Smoothened (SMO) protein levels. Moreover, the tumidulin activity was not observed in the presence of Gli and SMO inhibitors. Together, these results demonstrate for the first time that tumidulin is a potent inhibitor of colorectal cancer cell stemness.


Author(s):  
Nikolay Mazov ◽  
◽  
Vadim Gureyev ◽  
◽  
◽  
...  

Twenty two science Russian periodicals in informatics and library studies are selected for the bibliometrical analysis of key journal indicators, including publication activity of the same journals’ editorial staff. For the first time for domestic journals, the study reveals hidden self-citation when editorial members include links to their journal from other publications. The available instruments of scientometrical databases, including Web of Science and Scopus, and the national system Russian Science Citation Index do not enable to identify this form of self-citation. The mentioned manipulations are aimed at boosting journal rating. In several cases, intensive and unjustified citation by journals’ editorial staff in other periodicals which we consider the violation of publication ethical principles, is revealed.


2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Xiaoli Ren ◽  
Jianbiao Xiao ◽  
Wanning Zhang ◽  
Feifei Wang ◽  
Yongrong Yan ◽  
...  

AbstractIn colorectal cancer (CRC), overt metastases often appear after years of latency. But the signals that cause micro-metastatic cells to remain indolent, thereby enabling them to survive for extended periods of time, are unclear. Immunofluorescence and co-immunoprecipitation assays were used to explore the co-localization of CCL7 and CCR2. Immunohistochemical (IHC) assays were employed to detect the characters of metastatic HT29 cells in mice liver. Flow cytometry assays were performed to detect the immune cells. Bruberin vivo MS FX Pro Imager was used to observe the liver metastasis of CRC in mice. Quantitative real-time PCR (qRT-PCR) and western blot were employed to detect the expressions of related proteins. Trace RNA sequencing was employed to identify differentially expressed genes in MDSCs from liver micro-M and macro-M of CRC in mice. Here, we firstly constructed the vitro dormant cell models and metastatic dormant animal models of colorectal cancer. Then we found that myeloid-derived suppressor cells (MDSCs) were increased significantly from liver micro-metastases to macro-metastases of CRC in mice. Moreover, monocytic MDSCs (Mo-MDSC) significantly promoted the dormant activation of micro-metastatic cells compared to polymorphonuclear MDSCs (PMN-MDSC). Mechanistically, CCL7 secreted by Mo-MDSCs bound with membrane protein CCR2 of micro-metastatic cells and then stimulated the JAK/STAT3 pathway to activate the dormant cells. Low-dose administration of CCL7 and MDSCs inhibitors in vivo could significantly maintain the CRC metastatic cells dormant status for a long time to reduce metastasis or recurrence after radical operation. Clinically, the level of CCL7 in blood was positively related to the number of Mo-MDSCs in CCR patients, and highly linked with the short-time recurrence and distant metastasis. CCL7 secreted by Mo-MDSCs plays an important role in initiating the outgrowth of metastatic latent CRC cells. Inhibition of CCL7 might provide a potential therapeutic strategy for the prevention of metastasis recurrence.


2013 ◽  
Vol 2 (5) ◽  
pp. 383-385
Author(s):  
Sofya Pintova ◽  
Randall F Holcombe

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