• YAKHAK HOEJI
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• v.53 no.4
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• pp.184-188
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• 2009

Fluorouracil (5-FU) is one of the most widely used chemotherapeutic drugs in the treatment of advanced colorectal cancer patients. Capsaicin (N-vanillyl-8-methyl-alpha-nonenamide), a spicy component of hot pepper, is a homovanillic acid derivative that preferentially induces cancer cells to undergo apoptosis. The purpose of the present study is to examine whether capsaicin enhances the anticancer effect of 5-fluorouracil in HT-29 human colon cancer cells by inducing apoptosis, and whether PPARgamma is involved in the capsaicin action in combination treatment with 5-FU. Treatment of the cells with either 5-FU or capsaicin alone for 48 h had little effect on the cell viability up to $50{\mu}M$ concentration, whereas co-treatment of the cells with capsaicin in the presence of 5-FU for 48 h significantly decreased the cell viability in a concentration-dependent manner. In addition, caspase-3 activity, a marker enzyme for apoptosis, was significantly increased by the combined treatment with 5-FU and capsaicin compared to the 5-FU or capsaicin alone treatment. Also, treatment with troglitazone, a peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) agonist, further enhanced the effect of the combination treatment on the cell viability and caspase-3 activity, and bisphenol A diglycidyl ether (BADGE), a $PPAR{\gamma}$ antagonist, blocked the effect of the combination treatment. These results suggest that the combination treatment of HT-29 cells with 5-FU and capsaicin induces apoptotic cell death at relatively low concentration than each drug alone, and the combination treatment may be associated with the $PPAR{\gamma}$ pathway activation.

• The Korean Journal of Food And Nutrition
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• v.5 no.1
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• pp.13-22
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• 1992

This study was divised to observe the inhibitory effect of growth rate of human colon cancer cells by Eucommial leaf extract, in vitro. Three species of human colon cancer cells, HRT-18, HCT-48 and HT-29, were used for the experiment. Each extract of Eucommial leaf was prepared by extraction with water, 95% alcohol, acetone, chloroform and petroleum ether, and then the inhibitory effect of each extract on the growth rate of cells was compared with control group and each other. The experimental results obtained are summarized as follows; 1. Inhibitory effects on growth rate of human colon cancer fells were strongest in the petroleum ether extract and next in the chloroform extract. 2. Inhibitory effects on the growth rate of the cancer cells by extracts of water, 95% alcohol and acetone were weaker than that of petroleum ether and chloroform. 3. Inhibitory effect of each extract on the cancer cell growth was shown most strong activity in HT-29, and was in order of HRT 18 and HCT-48. In view of the results, it could be suggested that inhibitory effects of non-polar solvent's extracts against the cancer cell growth were more stronger than that of polar solvents and the effects were indicated difference according to the species of the cells.

• Journal of Nutrition and Health
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• v.41 no.1
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• pp.13-21
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• 2008

To determine whether indol-3-carbinol (BC, $C_9H_9NO$), an autolysis product of a glucosinolate and a glucobrassicin in vegetables, regulated tight junction proteins (TJ) and suppressed cell invasion in colon cancer cells, this experiment was performed. Our results indicate that I3C inhibit cell growth of HT-29 cells in a dose (0, 50, $100{\mu}M$) and time (0, 24 and 48h) dependent manner. Using the wound healing and matrigel invasion study, respectively, BC inhibits the cell motility and invasion of the ovarian cancer cell line. The TEER values were increased in HT-29 cells grown in transwells treated with BC, reversely, paracellular permeability was decreased in those of condition. Claudin-1, claudin-5, ZO-1 and occuldin have been shown to be positively expressed in HT-29 coloncancer cells. I3C occurs concurrently with a significant decrease in the levels of those of proteins in HT-29 cells. But E-cadherin level in the HT-29 was increased by I3C. The reduction of claudin-1 and claudin-5 protein levels occurred post-transcriptionaly since their mRNA levels are no difference by I3C. Therefore, our results suggest that I3C may be expected to inhibit cancer metastasis and invasion by tighten the cell junction and restoring tight junction in colon cancer cell line, HT-29.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.1
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• pp.75-82
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• 1999

It has been reported that activation of sphingomyelin pathway and nonsteroidal anti-inflammatory drugs (NSAIDS) inhibit the promotion of colon carcinoma. Ceramide, a metabolite of sphingomyelin, and indomethacin were shown to induce apoptosis in colon carcinoma cells. However, the mechanisms of ceramide- and indomethacin-induced apoptosis in the colon carcinoma cells are not clearly elucidated. Recent studys showed that indomethacin-induced apoptosis in colon cancer cells through the cyclooxygenase-independent pathways, and that may be mediated by generation of ceramide. In this study, we compared effects of ceramide and indomethacin on important modulators of apoptotic processes in HT29 cells, a human colon cancer cell line. Ceramide and indomethacin induced apoptosis dose- and time- dependently. Ceramide and indomethacin increased stress-activated protein kinase (SAPK) activity, and decreased mitogen-activated protein kinase (MAPK) activity. The expression of Bak was increased by the treatment of ceramide and indomethacin. The expression of other Bcl-2 related proteins (Mcl-1, $Bcl-X_L,$ Bax) which were known to be expressed in colon epithelial cells was not changed during the ceramide- and indomethacin-induced apoptosis. Our results suggest that ceramide and indomethacin share common mechanisms for induction of apoptosis in HT29 cells.

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.211-217
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• 2011

Panax ginseng CA Meyer, a herb from the Araliaceae, has traditionally been used as a medicinal plant in Asian countries. Ginseng extract fermented by ginsenoside-${\beta}$-glucosidase treatment is enriched in ginsenosides such as Rh2 and Rg3. Here we show that a fermented ginseng extract, BST204, has anti-proliferative and anti-invasive effects on HT-29 human colon cancer cells. Treatment of HT-29 cells with BST204 induced cell cycle arrest at $G_1$ phase without progression to apoptosis. This cell cycle arrest was accompanied by up-regulation of tumor suppressor proteins, p53 and p21$^{WAF1/Cip1}$, down-regulation of the cyclin-dependent kinase/cyclins, Cdk2, cyclin E, and cyclin D1 involved in $G_1$ or $G_1/S$ transition, and decrease in the phosphorylated form of retinoblastoma protein. In addition, BST204 suppressed the migration of HT-29 cells induced by 12-O-tetradecanoylphorbol-13-acetate, which correlated with the inhibition of metalloproteinase-9 activity and extracellular signal-regulated kinase activity. The effects of BST204 on the proliferation and the invasiveness of HT-29 cells were similar to those of Rh2. Taken together, the results suggest that fermentation of ginseng extract with ginsenoside-${\beta}$-glucosidase enhanced the anti-proliferative and the anti-invasive activity against human colon cancer cells and these anti-tumor effects of BST204 might be mediated in part by enriched Rh2.

• Biomolecules & Therapeutics
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• v.23 no.3
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• pp.225-232
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• 2015

We identified a novel Akt signaling mechanism that mediates fucoidan-induced suppression of human colon cancer cell (HT29) proliferation and anticancer effects. Fucoidan treatment significantly inhibited growth, induced G1-phase-associated upregulation of p21WAF1 expression, and suppressed cyclin and cyclin-dependent kinase expression in HT29 colon cancer cells. Additionally, fucoidan treatment activated the Akt signaling pathway, which was inhibited by treatment with an Akt inhibitor. The inhibition of Akt activation reversed the fucoidan-induced decrease in cell proliferation, the induction of G1-phase-associated p21WAF1 expression, and the reduction in cell cycle regulatory protein expression. Intraperitoneal injection of fucoidan reduced tumor volume; this enhanced antitumor efficacy was associated with induction of apoptosis and decreased angiogenesis. These data suggest that the activation of Akt signaling is involved in the growth inhibition of colon cancer cells treated with fucoidan. Thus, fucoidan may serve as a potential therapeutic agent for colon cancer.

• Journal of Nutrition and Health
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• v.33 no.1
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• pp.80-85
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• 2000

This study was undertaken to investigate the inhibitory effects of propolis on the in vitro proliferation of human colon(HT-29) and hepatoma(HepG2) cancer cell lines. The growth of the HT-29 and HepG2 cells was respectively inhibited by the administration of propolis in a concentration response-dependent manner. The distributions of HT-29 and HepG2 cells cultured in the medium containing propolis were shifted to the smaller sizes, and then HT-29 and HepG2 cells were shrunken under microscopic observations. The progression of cell cycle from G1 to S phase was significantly inhibited by propolis in the HT-29 and HepG2 cell lines, respectively. Those observations suggest that propolis has anticancer effect against some of cancer cell lines in vitro. (Korean J Nutrition 33(1) : 80-85, 2000)

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3767-3772
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• 2014

Introduction: MicroRNAs have emerged as post-transcriptional regulators that are critically involved in tumorigenesis. This study was designed to explore the effect of miRNA 133b on the proliferation and expression of TBPL1 in colon cancer cells. Methods: Human colon cancer SW-620 cells and human colon adenocarcinoma HT-29 cells were cultured. MiRNA 133b mimcs, miRNA 133b inhibitors, siRNA for TBPL1 and scrambled control were synthesized and transfected into cells. MiR-133b levels in cells and CRC tumor tissue was measured by real-time PCR. TBPL1 mRNA was detected by RT-PCR. Cell proliferation was studied with MTT assay. Western blotting was applied to detect TBPL1 protein levels. Luciferase assays were conducted using a pGL3-promoter vector cloned with full length of 3'UTR of human TBPL1 or 3'UTR with mutant sequence of miR-133b target site in order to confirm if the putative binding site is responsible for the negative regulation of TBPL1 by miR-133b. Results: Real time PCR results showed that miRNA 133b was lower in CRC tissue than that in adjacent tissue. After miR-133b transfection, its level was elevated till 48h, accompanied by lower proliferation in both SW-620 and HT-29 cells. According to that listed in http://www.targetscan.org, the 3'-UTR of TBPL1 mRNA (NM_004865) contains one putative binding site of miR-133b. This site was confirmed to be responsible for the negative regulation by miR-133b with luciferase assay. Further, Western blotting and immunohistochemistry both indicated a higher TBPL1 protein expression level in CRC tissue. Finally, a siRNA for TBPL1 transfection obviously slowed down the cell proliferation in both SW-620 and HT-29 cells. Conclusion: MiR-133b might act as a tumor suppressor and negatively regulate TBPL1 in CRC.

• Journal of Microbiology and Biotechnology
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• v.17 no.9
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• pp.1546-1549
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• 2007

Chitosan oligosaccharide (COS, 3 kDa

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6549-6556
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• 2015

The PI3K-Akt-mTOR, $Wnt/{\beta}$-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, $Wnt/{\beta}$-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with $IC_{50}$ values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, ${\beta}$-catenin, $Gsk3{\beta}$, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, $Wnt/{\beta}$ catenin signaling pathways and induction of apoptosis pathway.