scholarly journals Suppression of ID1 expression in colon cancer cells increases sensitivity to 5-fluorouracil

2017 ◽  
Vol 64 (2) ◽  
Author(s):  
Tomasz Przybyła ◽  
Monika Sakowicz-Burkiewicz ◽  
Izabela Maciejewska ◽  
Hanna Bielarczyk ◽  
Tadeusz Pawełczyk
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Thymidine Phosphorylase ◽  
Dihydropyrimidine Dehydrogenase ◽  
Mrna Level ◽  
Colon Cancer Cells ◽  
Altered Expression ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Ht 29

Adjuvant chemotherapy with 5-fluorouracil remains the basic treatment for patients with advanced colorectal carcinoma. The major obstacle in successful treatment is an ability of CRC cells to acquire chemoresistance. Here we examined the impact of ID1 silencing on the sensitivity of CRC cells to 5-FU. To suppress ID1 expression in HT-29 and HCT-116 cells the cells were transduced with a lentiviral vector carrying the ID1 silencing sequence. Cells with silenced ID1 showed altered expression of epithelial and mesenchymal markers and exhibited increased proliferation rate compared to the parental cells. HCT-116 cells with suppressed ID1 became sensitized to 5-FU and this was not observed in HT-29 cells. Silencing ID1 resulted in altered expression of genes encoding enzymes metabolizing 5-FU. HT-29 cells with suppressed ID1 had significantly reduced mRNA level for thymidine phosphorylase, uridine-cytydine kinase 2 and dihydropyrimidine dehydrogenase. ID1 suppression in HCT-116 cells resulted in an increase of mRNA level for thymidine phosphorylase, thymidyne kinase and uridine-cytydine kinase 2 with concurrent drop of dihydropyrimidine dehydrogenase and thymidylate synthetase mRNA levels. In conclusion ID1 expression impacts the sensitivity of colon cancer cells to 5-FU and may be considered as potential predictive marker in CRC treatment.

scholarly journals Limonene and BEZ 235 inhibits growth of COLO-320 and HCT-116 colon cancer cells

2016 ◽  
Vol 8 (3) ◽  
pp. 89 ◽  
Author(s):  
Raja Ratna Reddy Yakkanti ◽  
P Chandra Sekhar ◽  
K Bharath Nandhan Reddy ◽  
S Ramamoorthy ◽  
S Ranga Suresh ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Colon Cancer Cells ◽  
Wild Type ◽  
Anticancer Effects ◽  
Clonogenic Potential ◽  
Hct 116 ◽  
Cancer Types ◽  
Hct 116 Cells ◽  
Preclinical And Clinical Studies

<p>D-Limonene is a dietary monoterpene with significant anticancer activity against many cancer types in preclinical and clinical studies. The study is designed to investigate synergistic anticancer effects of limonene and BEZ235 combination in COLO-320 and HCT-116 colon cancer cells. Cells were treated with both the drugs alone and in combination and the effects on cell viability; cell migration and clonogenic potential were examined. Results show that both drugs exhibited dose and time dependant cytotoxicity on the cell lines tested. CompuSyn analysis of the drug combination effects revealed the strong synergistic interaction of the combination. Our results also indicate that COLO-320 cells were more sensitive for anticancer effects of the drugs than HCT-116 cells. The presence of Ras and PI3K mutations in HCT-116 cells could possibly be one of the main reasons for the observed outcome as compared to the wild type expressions of them in COLO-320 cells.</p>

Abstract 5041: Aspirin acetylates and activates p53 in HT-29 and HCT-116 colon cancer cells

2010 ◽  
Author(s):  
Lloyd F. Alfonso ◽  
Raghavender Chivukula ◽  
Srinivasan Marimuthu ◽  
Jayarama B. Gunaje
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Colon Cancer Cells ◽  
Hct 116 ◽  
Ht 29

Induction of p53 contributes to apoptosis of HCT-116 human colon cancer cells induced by the dietary compound fisetin

2009 ◽  
Vol 296 (5) ◽  
pp. G1060-G1068 ◽  
Author(s):  
Do Y. Lim ◽  
Jung Han Yoon Park
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Death Receptor ◽  
Parp Cleavage ◽  
Caspase 8 ◽  
Colon Cancer Cells ◽  
Protein Levels ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Induced Apoptosis

Fisetin, or 3,3′,4′,7-tetrahydroxyflavone, is present in fruits and vegetables and has been previously reported to inhibit the proliferation of a variety of cancer cells (Lu X, Jung J, Cho HJ, Lim do Y, Lee HS, Chun HS, Kwon DY, Park JH. J Nutr 135: 2884–2890, 2005). We have demonstrated in a previous work that 20–60 μmol/l fisetin inhibits cyclin-dependent kinase activities resulting in cell cycle arrest in HT-29 colon cancer cells. In the present study, we attempted to characterize the mechanisms by which fisetin induces apoptosis in HCT-116 cells. DNA condensations, cleavage of poly(ADP-ribose) polymerase (PARP), and cleavage of caspases 9, 7, and 3 were induced in HCT-116 cells treated with 5–20 μmol/l of fisetin. Fisetin induced a reduction in the protein levels of antiapoptotic Bcl-xL and Bcl-2 and an increase in the levels of proapoptotic Bak and Bim. Fisetin did not affect the Bax protein levels, but induced the mitochondrial translocation of this protein. Fisetin also enhanced the permeability of the mitochondrial membrane and induced the release of cytochrome c and Smac/Diablo. Additionally, fisetin caused an increase in the protein levels of cleaved caspase-8, Fas ligand, death receptor 5, and TNF-related apoptosis-inducing ligand, and the caspase-8 inhibitor Z-IETD-FMK suppressed fisetin-induced apoptosis and the activation of caspase-3. Furthermore, fisetin increases p53 protein levels, and the inhibition of p53 expression by small interference RNA resulted in a decrease in the fisetin-induced translocation of Bax to the mitochondria, release of mono- and oligonucleosome in the cytoplasm, and PARP cleavage. These results show that fisetin induces apoptosis in HCT-116 cells via the activation of the death receptor- and mitochondrial-dependent pathway and subsequent activation of the caspase cascade. The induction of p53 results in the translocation of Bax to the mitochondria, which contributes to fisetin-induced apoptosis in HCT-116 cells.

Annona muricata leaves induce G1 cell cycle arrest and apoptosis through mitochondria-mediated pathway in human HCT-116 and HT-29 colon cancer cells

2014 ◽  
Vol 156 ◽  
pp. 277-289 ◽  
Author(s):  
Soheil Zorofchian Moghadamtousi ◽  
Hamed Karimian ◽  
Elham Rouhollahi ◽  
Mohammadjavad Paydar ◽  
Mehran Fadaeinasab ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Annona Muricata ◽  
Colon Cancer Cells ◽  
Cycle Arrest ◽  
Hct 116 ◽  
G1 Cell Cycle Arrest ◽  
Ht 29

Sphingoid Bases and Ceramide Induce Apoptosis in HT-29 and HCT-116 Human Colon Cancer Cells

2002 ◽  
Vol 227 (5) ◽  
pp. 345-353 ◽  
Author(s):  
Eun Hyun Ahn ◽  
Joseph J. Schroeder
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Human Colon ◽  
Protective Role ◽  
Colon Cancer Cells ◽  
Sphingoid Bases ◽  
Human Colon Cancer ◽  
Hct 116 ◽  
Human Colon Cancer Cells ◽  
Ht 29

Complex dietary sphingolipids such as sphingomyelin and glycosphingolipids have been reported to inhibit development of colon cancer. This protective role may be the result of turnover to bioactive metabolites including sphingoid bases (sphingosine and sphinganine) and ceramide, which inhibit proliferation and stimulate apoptosis. The purpose of the present study was to investigate the effects of sphingoid bases and ceramides on the growth, death, and cell cycle of HT-29 and HCT-116 human colon cancer cells. The importance of the 4,5-trans double bond present in both sphingosine and C2-ceramide (a short chain analog of ceramide) was evaluated by comparing the effects of these lipids with those of sphinganine and C2-dihydroceramide (a short chain analog of dihydroceramide), which lack this structural feature. Sphingosine, sphinganine, and C2-ceramide inhibited growth and caused death of colon cancer cells in time-and concentration-dependent manners, whereas C2-dihydroceramide had no effect. These findings suggest that the 4,5-trans double bond is necessary for the inhibitory effects of C2-ceramide, but not for sphingoid bases. Evaluation of cellular morphology via fluorescence microscopy and quantitation of fragmented low-molecular weight DNA using the diphenylamine assay demonstrated that sphingoid bases and C2-ceramide cause chromatin and nuclear condensation as well as fragmentation of DNA, suggesting these lipids kill colon cancer cells by Inducing apoptosis. Flow cytometric analyses confirmed that sphingoid bases and C2-ceramide increased the number of cells in the A0 peak indicative of apoptosis and demonstrated that sphingoid bases arrest the cell cycle at G2/M phase and cause accumulation in the S phase. These findings establish that sphingoid bases and ceramide induce apoptosis In colon cancer cells and implicate them as potential mediators of the protective role of more complex dietary sphingolipids in colon carcinogenesis.

scholarly journals ID: 1029 Effects of carnosine on regulation of migration and invasion in human colorectal cancer cells

2017 ◽  
Vol 4 (S) ◽  
pp. 104 ◽  
Author(s):  
Po-Yu Lai ◽  
Shu-Chen Hsieh ◽  
Chih-Chung Wu ◽  
Shu-Ling Hsieh
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Human Colon ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Human Colon Cancer Cells

Colorectal cancer is the third most commonly diagnosed cancer in the word. Carnosine is an endogenous dipeptide found in vertebrate skeletal muscles. It is known to have anti-fatigue, antioxidative, antihypertensive, antidiabetic, and cancer inhibiting effects. However, little research has been done regarding its influence on the metastasis of colon cancer. This study cultivated HCT-116 human colon cancer cells as a test model in order to investigate the impact of carnosine on the migration and invasion of human colon cancer cells. The results showed that 48-hour treatments of HCT-116 cells with 0.5, 1, or 5 mM carnosine each significantly inhibited the migration ability of the cells (P < 0.05). The 48-hour treatments with 0.5, 1, or 5 mM carnosine were also found to significantly reduce MMP-9 activity (P < 0.05), but not MMP-2 expression. Furthermore, when HCT-116 cells treated with 1 or 5 mM carnosine, invasion ability are significantly decreased and significantly increased E-cadherin expression (P < 0.05). On the other hand, the protein of TIMP-1, an inhibitor of MMP-9, is signification increased after 1 or 5 mM carnosine treatment (P<0.05). In addition, the u-PA protein level are significantly decreased after carnosine treatment. The results indicate that carnosine can regulate the migration and invasion by regulating MMPs and its regulator molecular expression in HCT-116 cells.

scholarly journals Schlafen-3 decreases cancer stem cell marker expression and autocrine/juxtacrine signaling in FOLFOX-resistant colon cancer cells

2011 ◽  
Vol 301 (2) ◽  
pp. G347-G355 ◽  
Author(s):  
Phil-Sun Oh ◽  
Vaishali B. Patel ◽  
Matthew A. Sanders ◽  
Shailender S. Kanwar ◽  
Yingjie Yu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Stem Cell ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Stem Cell Marker ◽  
Drug Transporter ◽  
Colon Cancer Cells ◽  
Hct 116 ◽  
Ht 29

We have previously demonstrated that expression of the novel gene schlafen-3 (Slfn-3) correlates with intestinal epithelial cell differentiation (Patel VB, Yu Y, Das JK, Patel BB, Majumdar AP. Biochem Biophys Res Commun 388: 752–756, 2009). The present investigation was undertaken to examine whether Slfn-3 plays a role in regulating differentiation of FOLFOX-resistant (5-fluorouracil + oxaliplatin) colon cancer cells that are highly enriched in cancer stem cells (CSCs). Transfection of Slfn-3 in FOLFOX-resistant colon cancer HCT-116 cells resulted in increase of alkaline phosphatase activity, a marker of intestinal differentiation. Additionally, Slfn-3 transfection resulted in reduction of mRNA and protein levels of the CSC markers CD44, CD133, CD166, and aldehyde dehydrogenase 1 in both FOLFOX-resistant HCT-116 and HT-29 cells. This was accompanied by decreased formation of tumorosphere/colonosphere (an in vitro model of tumor growth) in stem cell medium and inhibition of expression of the chemotherapeutic drug transporter protein ABCG2. Additionally, Slfn-3 transfection of FOLFOX-resistant HCT-116 and HT-29 cells reduced Hoechst 33342 dye exclusion. Finally, Slfn-3 transfection inhibited the expression of transforming growth factor-α in both FOLFOX-resistant colon cancer cells, but stimulated apoptosis in response to additional FOLFOX treatment. In summary, our data demonstrate that Slfn-3 expression inhibits multiple characteristics of CSC-enriched, FOLFOX-resistant colon cancer cells, including induction of differentiation and reduction in tumorosphere/colonosphere formation, drug transporter activity, and autocrine stimulation of proliferation. Thus Slfn-3 expression may render colon CSCs more susceptible to cancer chemotherapeutics.

Requirement for store-operated calcium entry in sodium butyrate-induced apoptosis in human colon cancer cells

2011 ◽  
Vol 32 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Suxia Sun ◽  
Wenjun Li ◽  
He Zhang ◽  
Longying Zha ◽  
Yong Xue ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Butyric Acid ◽  
Sodium Butyrate ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Acetoxymethyl Ester ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Induced Apoptosis

The SOCE (store-operated Ca2+ entry) pathway plays a key role in both normal cells and cancerous cells. However, its molecular mechanism remains a long-lasting puzzle of Ca2+ signalling. In this paper, we provide evidence that butyric acid, a dietary fibre-derived short-chain fatty acid, induces apoptosis of colon cancer cells via SOCE signalling networks. We found that sodium butyrate (NaB) induces Ca2+ release from endoplasmic reticulum, which in turn causes extracellular Ca2+ influx in HCT-116 cells. The Ca2+ release and influx are important, because the addition of chelators, EGTA or BAPTA/AM [1,2-bis-(o-aminophenoxy)ethane-N,N,N′,N′-tetra-acetic acid tetrakis(acetoxymethyl ester)] respectively blocked NaB-induced apoptosis. Furthermore, down-regulation of STIM1 (stromal interaction molecule 1) by RNA interference or pharmacological blockade of the SOCC (store-operated Ca2+ channel) by 2-APB (2-aminoethoxydiphenyl borate) or SKF-96365 inhibited NaB-induced extracellular Ca2+ influx and apoptosis in HCT-116 cells. Thus we conclude that NaB triggers colon cancer cell apoptosis in an SOCE-dependent manner. This finding provides new insights into how butyric acid suppresses colon carcinogenesis.

scholarly journals Ellagic acid regulates Wnt/β-catenin signaling pathway and CDK8 in HCT 116 and HT 29 colon cancer cells

2015 ◽  
Vol 10 (1) ◽  
Author(s):  
Yang Fang ◽  
Hong Zhou ◽  
Jian-Fu Xia ◽  
Jie-Jun Lin ◽  
Ri-Zeng Li ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Ellagic Acid ◽  
Colon Cancer Cells ◽  
Hct 116 ◽  
Ht 29
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