• Title/Summary/Keyword: anticancer activities

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Effect of Lycopene on the Insulin-like Growth Factor-I Receptor Signaling Pathway in Human Colon Cancer HT-29 Cells (인간의 대장암 HT-29 세포주에서 라이코펜이 Insulin-like Growth Factor-I Receptor Signaling Pathway에 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.437-443
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    • 2003
  • Epidemiological data suggest that lycopene has anticancer activities in humans. Insulin-like growth factor-I receptor (IGF-IR) is a transmembrane tyrosine kinase that mediates the biological actions of IGFs and may play an active role in cancer progression. Because our previous in vitro studies have indicated lycopene inhibits HT-29 cell growth, the aim of this study was to determine whether lycopene induces apoptotic cell death and the inhibitory effect of lycopene on HT-29 cell growth is related to changes in IGF-IR levels and the receptor's intracellular signalling pathways. HT-29 cells were incubated for 4 days in serum-free medium in the presence of 0, 25, 50, or 100 $\mu$M lycopene, and the DNA fragmentation assay was performed. Cells treated with lycopene produced a distinct oligonucleosomal ladder with different sizes of DNA fragments, a typical characteristic of cells undergoing apoptosis. HT-29 cells were cultured for 4 days in serum-free medium in the presence of 0~100 $\mu$M lycopene and IGF-I (10nM) was added for 0~60 minutes immediately prior to lysate preparations. Western blot analysis of total lysates revealed that lycopene decreased the levels of IRS-1, Akt, phosphatidylinositol 3-kinase (PI3K), and IGF-IR $\beta$-subunit, and increased the levels of the IGF-IR precursor dose dependently. Lycopene also decreased IGF-I-induced phosphorylation of IGF-IR$\beta$, IRS-1 and Akt, which were, at least in part, due to decreased expression of these proteins. These results suggest that lycopene induces apoptosis of HT-29 cells by inhibiting IGF-IR signaling thereby interfering with an IGF-II-driven autocrine growth loop, which is known to exist in this cell line.

Effects of Chitosan Treatment on Changes of Soyasaponin Contents in Soybean Sprouts (키토산 처리가 콩나물의 Soyasaponin 함량변화에 미치는 효과)

  • Oh, Bong-Yun;Park, Bock-Hee;Ham, Kyung-Sik
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.5
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    • pp.584-588
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    • 2007
  • Elicitors are defined as substances that induce defense responses in plants, which include an increased synthesis of secondary metabolites. Saponin, one of the secondary metabolites, has various physiological effects such as anticancer, antioxidant, cholesterol-lowering activities, etc, in human. This study was carried out to find whether a treatment of soybean sprouts with chitosan as an elicitor, increases saponin contents. Saponin contents in soybean sprouts increased by the chitosan treatment during cultivation, reached the peak on the sixth day, and then decreased. A biosynthesis of group B soyasaponin appeared to be regulated differently. The content of soyasaponin I, a member of group B saponin, was the highest in 250 ppm chitosan-treated soybean sprouts, while the contents of soyasaponin II, III and IV were the highest in 1,000 ppm chitosan-treated soybean sprouts. The content of soyasaponin V changed little in soybean sprouts that had been treated with various concentration of chitosan.

Isolation of Anticarcinogenic Isoflavone-conjugated Glycoproteins from a Submerged Liquid Culture of Agaricus blazei Mycelia by the Autolysis Process (신령버섯균사체 액체배양물의 자가분해에 의한 항암성 isoflavone-conjugated glycoprotein 분리)

  • Kim, So Young;Kim, Young Suk;Jang, Joung Soon;Kim, Boh Hyun;Rakib, Abdur Md.;Kim, Gon Sup;Kim, Jeong Ok;Ha, Yeong Lae
    • Journal of Life Science
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    • v.24 no.12
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    • pp.1316-1324
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    • 2014
  • Most beta-glucans obtained from various fruit bodies of mushrooms and mushroom mycelial cultures have high-molecular weight glycoproteins, conjugated with beta-glucans. We report that isoflavone-conjugated glycolproteins (designated as gluvone) were isolated and exhibited stronger anticarcinogenic activities. Agaricus blazei mycelia (ABM) was cultured in a liquid medium containing soybean flakes for 14 days. The liquid culture was autolyzed by incubating at $53^{\circ}C$ (pH 5.5) for 3 h. A crude glycoprotein (CGP) fraction with a cytotoxic effect on a mouse ascite cancer cell line (S-180) and a human breast cancer cell line (MCF-7) was isolated from the autolyzed ABM cultures by 80% ethanol treatment. Gluvone was isolated from the CGP with Sephadex G-75 column chromatography. It exhibited a stronger anticancer effect than CGP against the S-180 cell-induced female ICR mouse ascites carcinogenesis. Gluvone with 9,400 daltons was identified as a glycoprotein conjugated with isoflavone. According to HPLC and GC analysis, in conjunction with $^1H$-NMR spectral analysis, it contained 60% carbohydrates (glucose, fructose, and ribose), 31% protein, and 2% isoflavone (daidzein and genistein), which is a novel material. These results indicate that a strong anticarcinogenic gluvone was isolated from the autolyzed product of a submerged liquid culture of ABM, suggesting that autolysis could be a useful tool to produce antitumor agents.

Anti-cancer Activity of Paclitaxel, Lenvatinib and Radiation Combination Therapy on Anaplastic Thyroid Cancer in Vitro and in Vivo (Paclitaxel, Lenvatinib 및 방사선 병용 요법의 역형성 갑상선암에서의 항암 작용)

  • Jun, Shiyeol;Kim, Soo Young;Kim, Seok-Mo;Park, Ki Cheong;Kim, Hee Jun;Chang, Ho Jin;Lee, Yong Sang;Chang, Hang-Seok;Park, Cheong Soo
    • Korean Journal of Head & Neck Oncology
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    • v.35 no.2
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    • pp.19-25
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    • 2019
  • Background/Objectives: Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the deadliest forms of thyroid cancer. The fatality rate for ATC is high, and the survival rate at one year after diagnosis is <20%. The present study aimed to investigate the anti-tumor activities of paclitaxel, radiation, and tyrosine kinase inhibitor (TKI) combined therapy in anaplastic thyroid cancer cells both in vitro and in vivo and explore its effects on apoptotic cell death pathways. Materials & Methods: ATC cell line was exposed to TKI, lenvatinib in the presence or absence of paclitaxel with radiation, and cell viability was determined by MTT assay. Effects of the combined treatment on cell cycle and intracellular signaling pathways were assessed by flow cytometry and western blot analysis. The ATC cell line xenograft model was used to examine the anti-tumor activity in vivo. Results: Our data revealed that the combined administration of paclitaxel, TKI, and radiation decreased cell viability in ATC cells, and also significantly increased apoptotic cell death in these cells, as demonstrated by the cleavage of caspase-3 and DNA fragmentation. This combination therapy reduced anti-apoptotic factor levels in ATC cells, while significantly decreasing tumor volume and increasing survival in ATC xenografts. Conclusion: These results indicate that administering the combination of paclitaxel, TKI, and radiation therapy may exert significant anticancer effects in preclinical models, potentially suggesting a new clinical approach for treating patients with ATC.

DNA Breakage by Salvianolic acid B in the Presence of Cu (II) (구리이온(II)이 존재할 때 Salvianolic acid B에 의한 DNA 절단)

  • Lee, Pyeongjae;Moon, Cheol;Choi, Yoon Seon;Son, Hyun Kyu
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.2
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    • pp.205-210
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    • 2018
  • Salvianolic acid B, which is a compound in the Salvia miltiorrhiza, has diverse biological activities, In particular, the antioxidative effects were reported to be involved in the protection of hepatocytes, neurons, and various cell types. On the other hand, some phenolic compounds, such as ferulic acid, which is regarded as an antioxidant, plays a pro-oxidative role in the specific transitional metal environment, which could explain the anticancer effect. This study examined the pro-oxidative effects of salvianolic acid B in the presence of $Cu^{2+}$. Treatment with both salvianolic acid B and $Cu^{2+}$ induced the transition of supercoiled DNA to the open circular or linear form but not in the sole salvianolic acid B or $Cu^{2+}$ treatments. Salvianolic acid B reduced the $Cu^{2+}$ to $Cu^+$ using neocuproine, a $Cu^+$ specific chelator. In addition, catalase, an enzyme that breaks down the $H_2O_2$ to water and molecular oxygen, inhibited the DNA breakage. $H_2O_2$, a reactive oxygen species, has detrimental effects on biological molecules, particularly DNA. Overall, the reduction of $Cu^{2+}$ by salvianolic acid B could lead to the production of $H_2O_2$ followed by DNA breakage. These results suggest that the pro-oxidative effects could be the one of the anti-cancer mechanisms of salvianolic acid B, which remains to be explained.

Screening of Potential Anticancer Compounds from Marketed Drugs: Aripiprazole, Haloperidol, Miconazole, and Terfenadine Inhibit Cytochrome P450 2J2 (시판 약물의 시토크롬 2J2 약물대사효소 저해능 탐색)

  • Liu, Kwang-Hyeon
    • Journal of Life Science
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    • v.21 no.11
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    • pp.1558-1564
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    • 2011
  • Cytochrome P450 2J2 (CYP2J2) plays important roles in the metabolism of endogenous metabolites such as arachidonic acid as well as therapeutic drugs. CYP2J2 is overexpressed in human cancer tissues and cancer cell lines, as well as in epoxyeicosatrienoic acids (EETs) and CYP2J2-mediated metabolites, and prevent apoptosis of cancer cells. This study aimed to screen marketed drugs for inhibitory potential on CYP2J2 isoforms using human liver microsomes. The initial screen isolated 4 compounds, from 120 marketed drugs, that inhibited the CYP2J2-mediated astemizole O-demethylation more than 50% in the following the order: haloperidol (75%) > terfenadine (56%) > aripiprazole (55%) > miconazole (52%). Miconazole strongly inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}$=11.2 ${\mu}M$) and terfenadine hydroxylation ($IC_{50}$=2.2 ${\mu}M$), and terfenadine also inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}$=13.6 ${\mu}M$) in a dose dependent manner. The present data suggest that these drugs are potential candidates for further evaluation for their anti-cancer activities.

Induction of Apoptosis and G2/M Cell Cycle Arrest by Cordycepin in Human Prostate Carcinoma LNCap Cells (Cordycepin에 의한 LNCap 인체 전립선 암세포의 apoptosis 및 G2/M arrest 유발)

  • Lee, Hye Hyeon;Hwang, Won Deok;Jeong, Jin-Woo;Park, Cheol;Han, Min Ho;Hong, Su Hyun;Jeong, Yong Kee;Choi, Yung Hyun
    • Journal of Life Science
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    • v.24 no.1
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    • pp.92-97
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    • 2014
  • Cordycepin, an active component originally isolated from the traditional medicine Cordyceps militaris, is a derivative of the nucleoside adenosine, which has been shown to possess a number of pharmacological properties, including antioxidant and anti-inflammatory activities, immunological stimulation, and antitumor effects. This study was conducted on cultured human prostate carcinoma LNCap cells to elucidate the possible mechanisms by which cordycepin exerts its anticancer activity, which, until now, has remained poorly understood. Cordycepin treatment of LNCap cells resulted in dose-dependent inhibition of cell growth and the induction of apoptotic cell death as detected by an MTT assay, cleavage of poly ADP-ribose polymerase, and annexin V-FITC staining. Flow cytometric analysis revealed that cordycepin resulted in G2/M arrest in cell cycle progression and downregulation of cyclin B1 and cyclin A expression in a concentration-dependent manner. Moreover, the incubation of cells with cordycepin caused a striking induction in the expression of the cyclin-dependent kinase (CDK) inhibitor p21Waf1/Cip1 without affecting the expression of the tumor suppressor p53. It also resulted in a significant increase in the binding of CDK2 and CDC2 to p21. These findings suggest that cordycepin-induced G2/M arrest and apoptosis in human prostate carcinoma cells is mediated through p53-independent upregulation of the CDK inhibitor p21.

Antioxidative, Antimutagenic and Cytotoxic Effects of Functional Food Manufactured from Fermented Soybean Extract (발효 콩을 주원료로 한 기능성 식품 추출물의 항산화성, 항돌연변이원성 및 세포독성 효과)

  • 최승필;오흥석;박종철;남기본;이득식;함승시
    • Food Science and Preservation
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    • v.11 no.2
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    • pp.214-220
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    • 2004
  • This study was carried out to determine the antioxidative, antimutagenic, and anticancer effects of functional food manufactured from fermented soybean(FFMFS) using DPPH free radical donating method, Ames test and cytotoxicity, respectively. FFMFS extracted with ethanol and then further fractionated to n-hexane, chloroform, ethyl acetate(EtOAc), butanol and water, stepwise. Among five fractions, the EtOAc fractions showed highest electron donating activities (31.6 $\mu\textrm{g}$/mL). The inhibition rate of ethanol extract(200 $\mu\textrm{g}$/plate) of FFMFS in the S. typhimurium TA100 strain showed 84.8% against the mutagenesis induced by MNNG. In addition, the suppression of EtOAc fractions with same concentration of FFMFS the S. typhimurium TA98 and TA100 strains showed 88.7% and 92.8% inhibition against Trp-P-l, respectively. The cytotoxic effects of FFMFS against the cell lines with human lung carcinoma(A549), human gastric carcinoma(AGS) and human breast adenocarcinoma(MCF-7) were inhibited with the increase of the extract concentration. The treatment of 1.0 mg/mL FFMFS of EtOAc fraction showed strong cytotoxicities of 84.5%, 88.7% and 85.6% against A549, AGS and MCF-7, respectively.

Anti-inflammatory Activities of Methanolic Extracts from Different Rose Cultivars (품종별 장미꽃 메탄올 추출물의 항염증 효과)

  • Lee, Seon-Mi;Li, Lin;Sung, Jeehye;Yang, Jinwoo;Kim, Younghwa;Jeong, Heon Sang;Lee, Junsoo
    • The Korean Journal of Food And Nutrition
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    • v.28 no.4
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    • pp.551-557
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    • 2015
  • The genus Rosa (Rosaceae) is an abundant source of phenolics and is traditionally used as a food supplement and as herbal medicine. Various plant phenolics are known to have anticancer, antioxidant, and anti-inflammatory properties. In this study, we investigated the anti-inflammatory effects of rose methanolic extracts (RMEs) from four different rose cultivars (Macarena, Onnuri, Oklahoma, and Colorado) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Our results demonstrated that pretreatment of REMs ($500{\mu}g/mL$) significantly reduced NO production by suppressing iNOS protein expression in LPS-stimulated cells. Anti-inflammatory effects by RMEs were observed in the following order: Oklahoma > Colorado > Onnuri > Macarena. Consistent with this finding, RMEs inhibited the translocation of $NF-{\kappa}B$ from the cytosol to the nucleus via the suppression of $I{\kappa}B{\alpha}$ phosphorylation and also inhibited LPS-stimulated $NF-{\kappa}B$ transcriptional activity. These findings suggest that RMEs exert anti-inflammatory actions and help to elucidate the mechanisms underlying the potential therapeutic values of RMEs. Therefore, RMEs could be regarded as a potential source of natural anti-inflammatory agents.

Identification and Determination of Dietary Fibers and Flavonoids in Pulp and Peel of Korean Tangerine (Citrus aurantium var.) (감귤과육 및 과피의 식이섬유와 플라보노이드 검색 및 정량)

  • Eun, Jong-Bang;Jung, Young-Min;Woo, Gun-Jo
    • Korean Journal of Food Science and Technology
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    • v.28 no.2
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    • pp.371-377
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    • 1996
  • Potential health promoting effects such as antiallergic, anti-inflammatory, antiviral, anticancer and anticarcinogenic properties have been ascribed to citrus flavonoids. Dietary fibers have also been used as functional food components due to the various beneficial physiological activities. Two kinds of flavonoids, naringin and hesperidin, were identified both in the pulp and in the peel of Korean tangerine. The contents of naringin and hesperidin in the pulp were 2.95 mg/100 g and 0.53 mg/100 g, respectively. However, the contents of naringin and hesperidin in the peel were much higher (10.77 mg/100 g and 38.90 mg/100 g) thanthose of two identified flavonoids in the pulp. The content of soluble dietary fiber (SDF) in the pulp of tangerine was 1.90%, insoluble dietary fiber (IDF) 0.37%, and total dietary fiber (TDF) 2.27% based on wet matter, respectively. The content of SDF was 1.09%, IDF 4.77% and TDF 1.86% in the peel of tangerine. The total pectin content was 1.53% in the pulp and 0.94% in the peel of tangerine. The peel of Korean tangerine, a by product in tangerine processing, would be a good source for the production of naringin, hesperidin and pectin.

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