• Title/Summary/Keyword: human colon cancer

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Anti-oxidative and Anti-cancer Activities of Methanol Extract of Machaerium cuspidatum (Machaerium cuspidatum 메탄올 추출물의 항산화 및 항암활성에 관한 연구)

  • Jin, Soojung;Oh, You Na;Park, Hyun-jin;Kwon, Hyun Ju;Kim, Byung Woo
    • Microbiology and Biotechnology Letters
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    • v.44 no.4
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    • pp.432-441
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    • 2016
  • Machaerium cuspidatum, a canopy liana, is a species of genus legume in the Fabaceae family and contributes to the total species richness in the tropical rain forests. In the present study, we investigated the antioxidative and anti-cancer effects of M. cuspidatum and its mode of action. The methanol extract of M. cuspidatum (MEMC) exhibited anti-oxidative activity with an $IC_{50}$ value of $1.66{\mu}g/ml$, and this was attributable to its 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity. MEMC also exhibited a cytotoxic effect and induced morphological changes in a dose-dependent manner in several cancer cell lines including human lung adenocarcinoma A549 cells, human hepatocellular carcinoma HepG2 cells, and human colon carcinoma HT29 cells. Moreover, MEMC treatment induced the accumulation of subG1 population, which is indicative of apoptosis in A549 and HepG2 cells. MEMC-induced apoptosis was confirmed by the increase in Annexin V-positive apoptotic cells and apoptotic bodies using Annexin-V staining and DAPI staining, respectively. Further investigation showed that MEMC-induced apoptosis was associated with the increase in p53 and Bax expression, and the decrease in Bcl-2 expression. In addition, MEMC treatment led to proteolytic activation of caspase-3, 8, and 9 and degradation of poly-ADP ribose polymerase (PARP). Taken together, these results suggest that MEMC may exert a beneficial anti-cancer effect by inducing apoptosis via both the extrinsic and intrinsic pathways in A549 and HepG2 cells.

Effects of Onion Flesh and Peel on Chemical Components, Antioxidant and Anticancer Activities (양파 육질 및 껍질의 화학성분과 항산화 및 항암 활성 비교)

  • Jang, Joo-Ri;Lim, Sun-Young
    • Journal of Life Science
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    • v.19 no.11
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    • pp.1598-1604
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    • 2009
  • In order to determine chemical components of onion flesh and peel, general nutrients, vitamin C, and total flavonoids were measured. Onion peel showed less moisture (14.3%) and no vitamin C compared to onion flesh. Onion peel contained more amounts of total flavonoids compared to onion flesh. In addition, the inhibitory effects of solvent extracts from onion flesh and peel on $H_2O_$-induced oxidative stress and growth of cancer cell lines (AGS human gastric adenocarcinoma and HT-29 human colon cancer cells) were investigated. Acetone with methylene chloride (A+M) and methanol (MeOH) extracts from onion flesh and peel appeared to significantly reduce the levels of intracellular reactive oxygen species (ROS) (p<0.05) and a greater antioxidant effect was observed in onion peel. Among fractions, 85% aq. methanol showed a higher protective activity against oxidative stress in both flesh and peel and there was no effect in the water and hexane fractions. The growth of cancer cells exposed to medium containing extracts and fractions from onion flesh and peel was inhibited dose-dependently. The growth of AGS was inhibited more in both flesh and peel compared to HT-29, and onion peel was more effective than onion flesh. Among fractions, 85% aq. methanol showed the greatest effect on growth inhibition in both flesh and peel. $IC_{50}$ values of 85% aq. methanol fraction from onion flesh and peel on AGS were 0.04 and 0.03 mg/ml, respectively, while those on HT-29 were 0.23 and 0.04 mg/ml. From our results, 85% aq. methanol fraction had an inhibitory effect against oxidative stress and growth of cancer cells, suggesting that it may contain biological active compounds.

Effects of Polyacetylenes in Ginseng on Activity of Enzymes Related to Post-translational Modification of Ras Protein and Effects of Petroleum Ether Extract of Ginseng on Progression of Cell Cycle (인삼의 polyacetylene 계 성분이 Ras 단백질 변형 효소의 활성에 미치는 영향과 인삼의 석유에텔 추출물이 세포주기에 미치는 영향)

  • 김동청;이지영;인만진;채희정;황윤경;황우익
    • Journal of Ginseng Research
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    • v.25 no.4
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    • pp.156-161
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    • 2001
  • We investigated the effects of polyacetylenes of ginseng on farnesyl protein transferase (FPTase) and carboxyl methyl transferase (CMTase) activities related to post-translational modification of Ras protein. We also investigated the effect of petroleum ether extract (PEE) of ginseng on progression of cell cycle. FPTase activity was respectively inhibited 16.2% by 10mM panaxynol and 21.3% by 10mM panaxydol, whereas CMTase activity was not inhibited by panaxynol or panaxydol. Treatment of PEE significantly reduced the numbers and size of human colon cancer cell (HT-29) and human liver cancer cell(HepG2) cultured, respectively. To investigate the mechanism of growth inhibition by PEE of ginseng, we analyzed the cell cycle progressions of PT-29 and HepG2 cells, respectively. We found that PEE significantly inhibited progression of cell cycle from G1 to S phase. These results suggest that anticancer effects of PEE were derived from the arrest of G1 phase in cell cycle progression.

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Fermentation process increased antimutagenic and in vitro anticancer effects during Kochujang manufacturing (고추장 제조시 발효가 항돌연변이 및 in vitro 항암효과에 미치는 영향)

  • Kim, Ji-Young;Liu, Fang-Fang;Lim, Yaung-Iee;Park, Kun-Young
    • Food Science and Preservation
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    • v.21 no.6
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    • pp.878-884
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    • 2014
  • Increased antimutagenic and in vitro anticancer effects were observed by the fermentation process during Kochujang manufacturing. In order to confirm the increased functionality, wheat grain, first fermented wheat grains (FFWG), second fermented wheat grains (SFWG), final fermented wheat grains (FiFWG), red pepper powder (RPP), and commercial Kochujang (CK) were prepared. Kochujang manufactured with final fermented wheat grains and red pepper powder were further fermented for 15 days and 30 days. The antimutagenic effects were determined by counting the number of revertants in Salmonella Typhimurium TA100 against N-methyl-N'-nitro-nitrosoguanidine (MNNG, 1.0mg/mL). The final fermented wheat grains (52% inhibition) showed higher antimutagenic effects than the wheat grain (34%), and the commercial Kochujang showed the highest antimutagenic effects (55%). We tested the inhibitory effect on the growth of HT-29 human colon carcinoma cells and AGS human gastric adenocarcinoma cells by using MTT (3-(4,5-dimethyl-thiazol)-2,5-diphenyltetrazolium bromide) assay. The results showed that increased fermentation process continually increased the growth inhibitory effect on both cancer cells. The further fermentation for 15 days of the Kochujang product also increased inhibitory growth of the AGS cancer cells. In conclusion, the methanol extract from fermented wheat grains and commercial Kochujang showed sequentially increased antimutagenic and in vitro anticancer activity, and thus the final commercial Kochujang revealed the highest effect.

Effect of Carotenoids on the Growth of HT-29 Human Colon Cancer Cells (Carotenoids가 인체의 대장암 세포인 HT-29 세포의 증식에 미치는 영향)

  • ;;;;Frederick Khachik
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.3
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    • pp.428-436
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    • 2003
  • Epidemiological studies have observed a negative association between increased consumption of green and yellow vegetables and cancer incidence. These vegetables contain carotenoids, which are reported to exhibit anticarcinogenic effects. Overexpression of ErbB2 and ErbB3 genes is a frequent event in several human cancers. The present study was performed to determine whether $\alpha$-carotene, $\beta$-carotene, lutein, or lycopene inhibits cell growth and to assess such an effect is related to changes in the levels of the ErbB receptor family and tile ErbB3 receptor signaling pathway in HT-29 cells. HT-29 cells were cultured in serum-free medium in the presence of various concentrations (0~100 $\mu$M) of the individual carotenoids. $\alpha$ -Carotene and lycopene significantly inhibited cell growth in a dose-dependent manner, whereas lutein slightly inhibited cell growth and $\beta$-carotene increased cell growth. Lycopene is more potent than $\alpha$ -carotene in inhibiting HT-29 cell growth. Lycopene inhibited DNA synthesis and induced apoptosis of HT-29 cells. The ErbB3 ligand heregulin (HRG) increased cell growth but did not prevent the lycopene-induced inhibition of cell growth. Lycopene decreased ErbB2 protein levels in a dose-dependent manner. Immunoprecipitation/Western blot studies revealed that lycopene inhibited HRG-induced phosphorylation of ErbB3, recruitment of the 985 regulatory subunit of phosphatidylinositol 3-kinase (PI3K) to the ErbB3 receptor, and phosphorylation of Akt. These results indicate that downregulation of ErbB2/ErbB3/PI3K/Akt signaling may be one of the mechanisms by which lycopene inhibits HT-29 cell pro-liferation and induces apoptosis.

Combined Treatment of Sodium Salicylate and Genistein Induces Incomplete Apoptosis and Necrosis in MCF-7 Multicellular Tumor Spheroids (MCF-7 MTS에서 sodium salicylate과 genistein 복합처리는 불완전한 세포사멸과 세포괴사를 유도한다)

  • Lee, Su-Yeon;Kim, Cho-Hee;Jeon, Hyun-Min;Ju, Min-Kyung;Kim, Min-Young;Jeong, Eui-Kyong;Park, Hye-Gyeong;Kang, Ho-Sung
    • Journal of Life Science
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    • v.22 no.9
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    • pp.1145-1151
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    • 2012
  • Aspirin and its deacetylated form, sodium salicylate (NaSal), have been shown to exert chemopreventive activities against many human cancers including those of the colon, lung, and breast. Previously, we showed that combined treatment of NaSal and genistein synergistically induced apoptosis in A549 lung cancer cells, indicating that these two natural chemicals could be used in combination for cancer therapy. In this study, we examined effects of NaSal/genistein combined treatment on other cancer cells and in three-dimensional multicellular tumor spheroid (MTS) and in an in vitro solid tumor model. We found that the combined treatment induces apoptosis in the HCT116 cells and the A549 cells, but not in the MCF-7 cells. Interestingly, the MCF-7 cells responded to the NaSal/genistein combined treatment by undergoing cell death when they were cultivated as MTS. The combined treatment induced apoptosis at an earlier stage in the MCF-7 MTS culture. However, when the MCF-7 MTS was cultivated for a longer period, it induced necrosis rather than apoptosis. We further found that the apoptotic pattern observed in MCF-7 MTS was incomplete: the chromatins were condensed and fragmented, but the nuclear membrane was still intact. Taken together, these results demonstrate that the NaSal/genistein combined treatment induces incomplete apoptosis and necrosis in the MCF-7 MTS culture system.

Growth Inhibitory Effect of Kimchi Prepared with Four Year-Old Solar Salt and Topan Solar Salt on Cancer Cells (토판염 및 4년 숙성 천일염으로 제조한 김치의 암세포 성장 억제 효과)

  • Yoon, Hae-Hoon;Chang, Hae-Choon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.7
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    • pp.935-941
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    • 2011
  • The growth inhibitory effects of kimchi prepared with solar salt were investigated. Chinese cabbages were brined with purified salt, four year-old solar salt, and Topan solar salt, and then mixed with other ingredients. The final salt concentration was adjusted to 2.2~2.4% (w/v) for each salt, and the kimchi was fermented at $7^{\circ}C$. When the acidity reached around 0.5~0.6%, the kimchi was used as a sample for further experimentation. MTT assay was used to measure the growth inhibitory effect of kimchi extracts (water, methanol) on BJ human foreskin normal cells, AGS human gastric adenocarcinoma cells, and HT-29 human colon carcinoma cells. Water extracts of all the kimchi samples showed growth inhibitory effects on cancer cells; however, there was no significant difference among the used salts. Methanol extracts of all the kimchi samples showed higher growth inhibitory effects compared to the water extracts. The methanol extracts of four year-old solar salt kimchi (AGS: 73%, HT-29: 48%) and Topan solar salt kimchi (AGS: 62%, HT-29: 46%) showed higher growth inhibitory effects than that of purified salt kimchi (AGS: 52%, HT-29: 39%). In addition, morphological changes of cancer cells (AGS, HT-29) and decreased cell numbers were observed when methanol extract of four year-old solar salt kimchi was treated to AGS and HT-29 cells. However, none of the kimchi extracts showed any growth inhibitory effect on BJ normal cells.

Comparative Studies of the Cytotoxic Effect of Four Different Sea Bream Species (Pagrus major, Acanthopagus schlegeli, Oplegnathus fasciatus, and Girella punctata) (4종 돔 추출물의 세포독성 효과 비교)

  • Hwang, Seong Yeon;Lim, Sun-Young
    • Journal of Life Science
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    • v.27 no.9
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    • pp.1064-1069
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    • 2017
  • This study compared the cytotoxic effect of extracts from four different sea bream species (Pagrus major, Acanthopagus schlegeli, Oplegnathus fasciatus, and Girella punctata) in human cancer cell lines. Cytotoxic activity against the growth of human gastric adenocarcinoma (AGS) and HT-29 human colon cancer cell lines was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Treatment with acetone/methylene chloride (A+M) and methanol (MeOH) extracts from the four sea bream species dose-dependently increased cytotoxicity against the growth of AGS and HT-29 cancer cells (p < 0.05). As shown by a cell viability assay, treatment with A+M and MeOH extracts from red sea bream (P. major) had the highest cytotoxic effect (p < 0.05) among the sea bream species. The IC50 values of an 85% aqueous methanol (85% aq. MeOH) fraction from red sea bream (P. major) against AGS and HT-29 cancer cells was 0.33 and 1.58 mg/ml, respectively, suggesting that the 85% aq. MeOH fraction had the highest cytotoxic effect among the fractions (p < 0.05). Our results demonstrate that four different sea bream species exhibited cytotoxic activity, as well as high-quality amino acids and fatty acids. Among the sea bream species, red sea bream (P. major) showed the greatest cytotoxic effect. The results could be used to improve nutrition information available to consumers.

Inhibition of $\alpha$-Glucosidase Activity by Quercetin (Quercetin에 의한 $\alpha$-glucosidase 활성 저해)

  • Lee, Dong-Sun;Kim, Jong-Guk;Lee, Sang-Han
    • Microbiology and Biotechnology Letters
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    • v.34 no.4
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    • pp.368-372
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    • 2006
  • Quercetin is a flavonoid molecule that is known to tie in various sources of natural products such as vegetables and fruits. It has been proven that quercetin plays a crucial role in the prevention of colon cancer as well as homeostasis as radical scavenger in human body. It is also well-known that glycosidases, including $\alpha$-glucosidase, are involved in a variety of degenerative metabolic disorders. In the course of screening useful $\alpha$-glucosidase inhibitors, we screened out quercetin as a $\alpha$-glucosidase inhibitor from chemical libraries. Quercetin was shown to be a reversible, slow-binding, and noncompetitive inhibitor of yeast a-glucosidase with a K$_i$ value of $6.3\times10^{-8}$ M when it was included with an enzyme mixture. Together, these results show that quercetin has potential in treating disorders including diabetes, although the further mechanistic study is needed.

In vivo anti-metastatic action of Ginseng Saponins is based on their intestinal bacterial metabolites after oral administration

  • Saiki, Ikuo
    • Journal of Ginseng Research
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    • v.31 no.1
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    • pp.1-13
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    • 2007
  • We found that the main bacterial metabolite M1 is an active component of orally administered protopanxadiol-type ginsenosides, and that the anti-metastatic effect by oral administration of ginsenosides may be primarily mediated through the inhibition of tumor invasion, migration and growth of tumor cells by their metabolite M1. Pharmacokinetic study after oral administration of ginsenoside Rb1 revealed that M1 was detected in serum for 24 h by HPLC analysis but Rb1 was not detected. M1, with anti-metastatic property, inhibited the proliferation of murine and human tumor cells in a time- and concentration-dependent manner in vitro, and also induced apoptotic cell death (the ladder fragmentation of the extracted DNA). The induction of apoptosis by M1 involved the up-regulation of the cyclin-dependent kinase(CDK) inhibitor $p27^{Kip1}$ as well as the down-regulation of a proto-oncogene product c-Myc and cyclin D1 in a time-dependent manner. Thus, M1 might cause the cell-cycle arrest (G1 phase arrest) in honor cells through the up/down-regulation of these cell-growth related molecules, and consequently induce apoptosis. The nucleosomal distribution of fluorescence-labeled M1 suggests that the modification of these molecules is induced by transcriptional regulation. Tumor-induced angiogenesis (neovascularization) is one of the most important events concerning tumor growth and metastasis. Neovascularization toward and into tumor is a crucial step for the delivery of nutrition and oxygen to tumors, and also functions as the metastatic pathway to distant organs. M1 inhibited the tube-like formation of hepatic sinusoidal endothelial (HSE) cells induced by the conditioned medium of colon 26-L5 cells in a concentration-dependent manner. However, M1 at the concentrations used in this study did not affect the growth of HSE cells in vitro.