• Title/Summary/Keyword: HCT

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Induction of Apoptosis in Human Colon Carcinoma HCT116 Cells Using a Water Extract of Lepidium virginicum L. (콩다닥냉이 추출물에 의한 HCT116 대장암세포의 사멸 유도에 관한 연구)

  • Chae, Yang-Hui;Shin, Dong-Yeok;Park, Cheol;Lee, Yong-Tae;Moon, Sung-Gi;Choi, Yung-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.5
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    • pp.649-659
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    • 2011
  • To examine the anti-cancer effects of Lepidium virginicum L., the anti-proliferative and pro-apoptotic effects of a water extract of L. virginicum leaves (WELVL) and of L. virginicum roots (WELVR) were investigated in HCT116 human colon carcinoma cells. The treatment of HCT116 cells with WELVL and WELVR resulted in the inhibition of growth and morphological changes in a concentration-dependent manner by inducing apoptosis. The growth inhibition and apoptosis induction by WELVR was stronger than that of WELVL thus, we determined that WELVR was the more optimal extract for this study. The increased apoptotic events in HCT116 cells caused by WELVR were associated with an up-regulation of Fas ligand, Bax, and Bad expression, a down-regulation of Bcl-2, Bcl-$_XL$, and Bid expression, and a decrease in the mitochondrial membrane potential (MMP, ${\Delta}{\psi}m$). WELVR treatment induced the proteolytic activation of caspase-3, -8, and -9, and the degradation of caspase-3 substrate proteins, such as poly (ADP-ribose) polymerase (PARP), ${\beta}$-catenin, and phospholipase C-${\gamma}1$ (PLC-${\gamma}1$). In addition, apoptotic cell death induced by WELVR was correlated with a down-regulation of inhibitors of the apoptosis protein (IAP) family, such as the X-linked inhibitor of apoptosis protein (XIAP), cIAP-1, and cIAP-2. These findings suggest that the WELVR-induced inhibition of cell proliferation is associated with the induction of apoptotic cell death. WELVR may be a potential chemotherapeutic agent for the control of HCT116 human colon carcinoma cells.

Apoptotic Effects of Curcumin and EGCG via Akt-p53 Signaling Pathway in HCT116 Colon Cancer Cells (HCT116 대장암 세포에서 Akt-p53 신호경로를 통한 커큐민과 EGCG의 apoptosis 효과)

  • Park, Song-Yi;Lee, Sol-Hwa;Park, Ock-Jin;Kim, Young-Min
    • Journal of Life Science
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    • v.21 no.1
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    • pp.89-95
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    • 2011
  • p53 is tumor suppressor gene that regulates apoptosis such as caspase-dependent and p21-mediated signaling pathways. PI3K/Akt is known to be over-activated in cancer cells. Akt activates many survival-related signals such as mTOR and COX-2. Inactivation of Akt would result in non-inhibition of p53 as well as induced apoptosis. In this study, we showed that curcumin and EGCG activate p53 via inhibition of the Akt signaling pathway. Treatments using curcumin and EGCG in different concentrations for 24 hr and 48 hr inhibited proliferation of HCT116 colon cancer cells and increased apoptotic cell death. Also, our data showed that curcumin and EGCG increased the p53 expression and decreased the p-Akt. Treatment of LY294002 (Akt inhibitor) resulted in decreased cell proliferation of cancer cells, while LY294002 treated with curcumin or EGCG showed a greater decrease of cell proliferation. In addition, inhibition of Akt induced p53 activation in HCT116 colon cancer cells. These results suggest that curcumin and EGCG induce apoptosis by inhibiting Akt and increase p53 in HCT116 colon cancer cells.

Effect of Fermented Compositions Containing Inonotus obliquus with Houttuynia cordata on Growth of Human AGS Gastric and HCT-15 Colon Cancer Cells (차가버섯과 어성초 함유 발효 조성물이 인체 위암 AGS 및 대장암 HCT-15 세포 생육에 미치는 영향)

  • Cha, Jae-Young;Jeon, Beong-Sam;Park, Jeong-Won;Moon, Jae-Chul;Cho, Young-Su
    • Applied Biological Chemistry
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    • v.47 no.2
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    • pp.202-207
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    • 2004
  • This study was performed to investigate the inhibitory effect of the water-extract from fermented compositions containing Inonotus obliquus with added Houttuynia cordata on the growth of either human AGS gastric and HCT-15 colon cancer cells or NIH3T3 normal mouse fibroblast cells. Cytotoxic activity on cancer cells was investigated by viable cell count, MTT assay and morphological observation. Mixtures of Inonotus obliquus with added Houttuynia cordata were fermented at $30{\sim}37^{\circ}C$, $50{\sim}60%$ humidity for 30 days, extracted with water, freeze dried, powered, and then dissolved in water for the experiment. In MTT assay, the fermented compositions exhibited inhibitory effects of 13, 25, 40, 67 and 78% for AGS and 22, 40, 50, 69 and 76% for HCT-15 at 0.16, 0.4, 0.8, 1.6 and 4.0 mg/ml, respectively. However, normal NIH3T3 cells were exhibited 86% survival under the same experimental condition. Fermented compositions showed highly inhibitory effect against human cancer cell line HCT-15 and AGS, but not on normal cell line NIH3T3.

Effect of Several Combined Preparation of Crude Drugs on the Adverse Effects of Anticancer Agent-Mitomycin C (항암제 Mitomycin C의 부작용에 대한 수종 복합생약의 영향)

  • Eun, Jae-Soon
    • Korean Journal of Pharmacognosy
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    • v.23 no.4
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    • pp.248-258
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    • 1992
  • The studies were conducted to investigate the combined effects of several combined preparation of crude drugs and mitomycin C(MMC). The combined effects on the proliferation of HepG2, A549, KHOS-Np, A431 and HeLa cells were estimated by MTT colorimetric assays. Sa Kunja Tang(SKT), Boyang Hwanoh Tang(BHT) and Hyulbu Choogo Tang(HCT) inhibited the proliferation of A549 and HeLa cell. The inhibitory action of MMC was increased by the combined treatment of SKT and MMC, and Sa Mul Tang(SMT) and MMC, respectively. When the mice were treated by MMC, the number of leukocyte was decreased significantly at the 3rd day, but recovered at the 7th day. In the groups of MMC treated with SKT or HCT, the number of leukocyte was increased significantly that the group of MMC treated only at the 1st and 3rd day. The combined treatment of SKT, SMT, BHT, HCT and MMC retained the spleen weight of mice at the level of normal mice, but decreased the thymus weight of mice. The combined treatment of SKT, SMT, BHT, HCT and MMC increased the number of PFC significantly than the MMC treated group. The combined treatment of SKT, SMT, BHT, HCT and MMC increased the T cell proliferation significantly thant the MMC treated group.

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The Effect of Potassium Cyanate (KCN) on Radiation Treatment of the Colorectal Cancer Cell Line, HCT 116

  • Chang, Jeong Hyun
    • Biomedical Science Letters
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    • v.19 no.2
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    • pp.98-104
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    • 2013
  • Radiation is one of the major therapy for the removal of cancer cells. The results of the radiation therapy depend on the radio-resistance of cancer cells. For the effective treatment in these radio-resistant cancers, the use of chemicals that act on cancer cells is known to enhance the cytotoxic effects of radiation therapy. In this study, I investigated the effect of potassium cyanate (KCN) on the irradiated-colorectal cancer cell line, HCT 116 cells. KCN induces the carbamylation of proteins and can change the biological activity of various human cells. To understand the effect of KCN on the radiosensitivity of HCT 116 cells, I examined alteration of the cell cycle, generation of reactive oxygen species (ROS), cell viability, apoptosis and intracellular signaling proteins in the irradiated cells with/without KCN treatment. Combination treatment caused significant increase in sub $G_0/G_1$ and ROS generation in HCT 116 cells. KCN inhibited the proliferation and cell viability in irradiated HCT 116 cells. KCN-induced apoptosis of irradiated cells was processed via the activation of caspase 3 and caspase 9. Apoptosis-associated signal proteins, including Bax and Bcl-2 were regulated by irradiation with KCN treatment. Taken together, these results may indicate that KCN enhances the radiosensitivity of radio-resistant cell and then has a synergistic effect on radiation therapy in colorectal cancer.

Sequential administration of camptothecin sensitizes human colon cancer HCT116 cells to paclitaxel via $p21^{Cip1/WAF1}$

  • Yoo, Jung-Min;Kim, Yun-Jin;Lee, Sung-Jae;Kim, Sang-Hoon
    • Animal cells and systems
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    • v.15 no.1
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    • pp.9-17
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    • 2011
  • Colorectal cancer is the third leading cause of cancer-related death in Western countries. Chemotherapeutic agents with different mechanisms of action have shown an increase in cure rates. In the present study, we investigated the effect of a combination of low concentration of paclitaxel (taxol, 5 nM) and topoisomerase 1 inhibitor camptothecin (CPT) on HCT116 colon cancer cells. Although the viability of cells treated with taxol alone was similar to that of control cells, sequential treatment with taxol and CPT exhibited high cytotoxicity. However, the opposite sequence of treatment did not exert cytotoxic effects on HCT116 cells. This enhanced cytotoxicity of the sequential combination therapy was the result of mitotic arrest, which increased the level of $p21^{Cip1/WAF1}$ through the p38 mitogen-activated protein kinase (MAPK) pathway. Knockdown by $p21^{Cip1/WAF1}$ siRNA or treatment with a p38 inhibitor reduced the viability of cells sequentially exposed to taxol and CPT. Taken together, a low taxol concentration in combination with CPT induced mitotic arrest in HCT116 cells, leading to synergistic cell death through enhanced expression of $p21^{Cip1/WAF1}$ and p38 MAPK pathway. Therefore, taxol could playa role as a sensitizer of CPT in colon cancer cells.

Dependency on p53 in Expression Changes of ATF3 and NAG-1 Induced by EGCG, Genistein, and Resveratrol (EGCG, genistein, resveratrol 처리에 의한 ATF3와 NAG-1 유전자 발현변화의 p53 의존성 분석)

  • Kim, Min-Jeong;Kim, Hyun-Ji;Seo, Yu-Mi;Lee, Eun-Joo;Kim, Jong-Sik
    • Journal of Life Science
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    • v.28 no.5
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    • pp.615-620
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    • 2018
  • Epigallocatechin-3-gallate (EGCG), one of catechins of green tea, has been known to possess anti-oxidation, anti-inflammation, and anti-cancer effects. The present study analyzed global gene expression changes in EGCG-treated HCT116 cells and p53-null HCT116 cells by oligo DNA microarray analysis. Among the differentially expressed genes in EGCG-treated HCT116 cells, four were selected that are known as tumor suppressor genes (activating transcription factor 3 [ATF3], cyclin dependent kinase inhibitor 1A [CDKN1A], DNA damage-inducible transcript 3 [DDIT3] and non-steroidal anti-inflammatory drug activated gene [NAG-1]) and their expression was compared to the expression of genes in p53-null HCT116 cells. We found that the expression of these genes was not dependent on their p53 status except for NAG-1, which was only up-regulated in HCT116. The results of RT-PCR and Western blot analysis showed that ATF3 up-regulation by EGCG was not affected by the presence of p53, whereas NAG-1 expression was not induced in p53-null HCT116 cells. We also detected ATF3 and NAG-1 expression changes through genistein and resveratrol treatment. Interestingly, genistein could not up-regulate ATF3 regardless of p53 status, but genistein could induce NAG-1 only in HCT116 cells. Resveratrol could significantly induce NAG-1 as well as ATF3 independent of p53 presence. These results indicate that EGCG, genistein and resveratrol may have different anti-cancer effects. Overall, the results of this study may help to increase our understandings of molecular mechanisms on anti-cancer activities mediated by EGCG, genistein and resveratrol in human colorectal cancer cells.

Effects of Houttuynia Cordata thunb on Antioxidative Activity against TCDD Damage (다이옥신 저해능에 대한 어성초의 항산화 활성 효과)

  • 하배진
    • Journal of Environmental Science International
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    • v.12 no.6
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    • pp.599-603
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    • 2003
  • This study investigated the effects of Houttuynia Cordata thunb(HCT) administration on the biochemical parameters of function in liver of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treated rats. Houttuynia Cordata thunb (200mg/kg) was administeres into rats intraperitoneally for four weeks , seven days after the injection of TCDD(1$\mu\textrm{g}$/kg). We examined the antioxidative enzymatic activity by measuring the level of AST, ALT , SOD and Catalase in serum and liver tissue of rats. HCT group showed 49% of inhibitive effect in AST activity compared to TANO group. ALT level of HCT group was decreased to the level of NO group. SOD and Catalase in TANO group were lower than in NO group, but SOD and Catalase in HCT group were increased by 46% and by 50% respectively compared to TANO group.

Antitumor Activities to Cytotoxicity of Phellinus linteus Ethanol Extract (목질진흙버섯 에탄을 추출물의 세포독성에 따른 항암활성)

  • 한기원;이수원;한광수;이대진;이병의;장원철
    • Toxicological Research
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    • v.19 no.2
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    • pp.147-152
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    • 2003
  • We investigated antitumor activities of the ethanol extract from mushroom Phellinus linteus and Phellinus baumii on mulberry, oak and elm. in vitro test, the ethanol extract of mushroom cultivated on oak of Phellinus linteus showed highest activities about SK-OV-3, HCT15, XF498, SK-MEL-2 and A549. SK-OV-3 cell line showed 100% cytotoxicity in 100 $\mu\textrm{g}$/ml and HCT15 (98.39%), XF498 (89.62%), SK-MEL-2 (84.07%) and A549 (79.92%) cytotoxicity respectively. Also $IC_{50}$ showed 3.99 $\mu\textrm{g}$/ml to SK-OV-3 cell line and HCT15 (4.37 $\mu\textrm{g}$/ml), A549 (5.48 $\mu\textrm{g}$/ml), SK-MEL-2 (6.72 $\mu\textrm{g}$/ml), XF 498 (6.88 $\mu\textrm{g}$/ml). As those results, cultivated oak of Phellinus linteus showed a very low $IC_{50}$ value against SK-OV-3, HCT15, XF498, SK-MEL-2 and A549 cancer cell lines.

The Effects of Houttuyniae Herba on the Mast Cell-mediated Inflammatory Responses (어성초(魚腥草)가 비만세포 매개 염증반응에 미치는 영향)

  • Lee, Hee-Joe;Kim, Kyung-Jun
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.22 no.2
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    • pp.60-73
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    • 2009
  • Objective : Houttuyniae Herba is widely used in oriental medicine as a remedy for inflammation. However, as yet there is no clear explanation of how Houttuyniae Herba affects the production of inflammatory cytokine. This study was to determine the effects of Essence extracted from Houttuynia cordata Thunb(HCT) on the mast cell-mediated inflammatory responses. Method : We measured the amount of inflammatory cytokine production induced by the phorbol myristate acetate (PMA) plus calcium ionophore(A23187) in the human mast cell line (HMC-1) incubated with various concentrations of HCT. The TNF-$\alpha$, IL-6 and IL-8 secreted protein levels were measured by the ELISA assay. The TNF-$\alpha$, IL-6 and IL-8 mRNA levels were measured by the RT-PCR analysis. Nuclear and cytoplasmic proteins were exmined by Western blot analysis. The NF-$\kappa$B promoter activity was examined by a luciferase assay. Result : HCT inhibited the PMA + A23187-induced TNF-$\alpha$, IL-6 expression and reduced mRNA of TNF-$\alpha$, IL-6 and IL-8. we observed that HCT suppressed the induction of NF-B activity. In addition, HCT suppressed PMA plus A23187-induced NF-$\kappa$B promoting activity. Conclusion : In this study, we have found that HCT is an inhibitor of NF-$\kappa$B and cytokines on the mast cell-mediated inflammatory responses.

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