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.

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.

scholarly journals The Indolic Diet-Derivative, 3,3′-Diindolylmethane, Induced Apoptosis in Human Colon Cancer Cells through Upregulation of NDRG1

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
A. Lerner ◽  
M. Grafi-Cohen ◽  
T. Napso ◽  
N. Azzam ◽  
F. Fares
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Colonic Cancer ◽  
P53 Gene ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Hct 116 ◽  
Poorly Differentiated ◽  
Induced Apoptosis

N-myc downstream regulated gene-1 participates in carcinogenesis, angiogenesis, metastases, and anticancer drug resistance. In the present study, we analyzed the expression pattern of N-myc downstream regulated gene-1 following treatment of human colonic cancer cell lines; HCT-116 (well differentiated with wild-type p53 gene) and Colo-320 (poorly differentiated with mutant p53 gene), with 3,3′-diindolylmethane, a well-established proapoptotic agent product derived from indole-3-carbinol. Treatment of Colo-320 and HCT-116 with 3,3′-diindolylmethane disclosed inhibition of cell viability in a dose-dependent manner, mediated through apoptosis induction. The increased expression of N-myc downstream regulated gene-1 was detected only in poorly differentiated colon cancer cells, Colo-320 cell line. Our results suggest that N-myc downstream regulated gene-1 expression is enhanced by 3,3′-diindolylmethane in poorly differentiated cells and followed by induction of apoptosis. 3,3′-diindolylmethane induced apoptosis may represent a new regulator of N-myc downstream regulated gene-1 in poorly differentiated colonic cancer cells.

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>

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 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 Growth Inhibition by Caffeic Acid, One of the Phenolic Constituents of Honey, in HCT 15 Colon Cancer Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Saravana Kumar Jaganathan
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Caffeic Acid ◽  
Mtt Assay ◽  
Time Dependent ◽  
Ros Generation ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Phenolic Constituents ◽  
Induced Apoptosis

Previous work from our laboratory showed that the mechanism of crude-honey induced apoptosis in colon cancer cells. Since phenolic constituents of honey were attributed to its apoptosis-inducing ability, we studied caffeic acid, one of the phenolic constituents of honey, induced effect on colon cancer cells. Antiproliferative effect of caffeic acid was estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. MTT assay signified the antiproliferative nature of caffeic acid against the HCT 15 colon cancer cells. A time-dependent inhibition of colony formation was evident with caffeic acid treatment. Cell-cycle analysis of caffeic acid- (CA-) treated cells indicated increasing accumulation of cells at sub-G1phase. Photomicrograph images of treated cells showed membrane blebbing and cell shrinkage. Yo-pro-1 staining of caffeic-acid-treated cells confirmed apoptosis in dose- and time-dependent manner. Increasing ROS generation and reduction in the mitochondrial membrane potential were also accompanied in the caffeic acid-induced apoptosis. This work will promote caffeic acid as a likely candidate in the chemoprevention of colon cancer.

Inhibition of autophagy by 3-MA potentiates purvalanol-induced apoptosis in Bax deficient HCT 116 colon cancer cells

2014 ◽  
Vol 328 (1) ◽  
pp. 87-98 ◽  
Author(s):  
Ajda Coker-Gurkan ◽  
Elif Damla Arisan ◽  
Pinar Obakan ◽  
Esin Guvenir ◽  
Narcin Palavan Unsal
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Colon Cancer Cells ◽  
Hct 116 ◽  
Induced Apoptosis
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