• Title/Summary/Keyword: antitumor efficacy

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Conversion of Acidic Polysaccharide and Phenolic Compound of Changed Ginseng by 9 Repetitive Steaming and Drying Process, and Its Effects of Antioxidation (인삼의 구증구포에 의한 산성다당체, 페놀성화합물의 변환 및 항산화능)

  • Kim, Do-Wan;Lee, Yun-Jin;Min, Jin-Woo;Kim, Yu-Jin;Rho, Young-Deok;Yang, Deok-Chun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.1
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    • pp.121-126
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    • 2009
  • Korean ginseng (Panax ginseng C. A. Meyer) has been used as an important medicinal plant in the Orient for a long time. It has been claimed that ginseng has many beneficial bioactive effects on human health, such as antitumor, antistress, antiaging and enhancing immune functions. Red ginseng possibly have new ingredients converted during steaming and dry process from fresh ginseng. In this study, pharmacological efficacy and ingredient conversion of ginseng by 9 repetitive steaming and drying process were investigated measuring conversion efficiency of acidic-polysaccharide, phenolic compounds and inhibition of peroxide lipides. It was found that acidic-polysaccarides were increased by heat treatment. In addition, maltol of phenolic compounds, strong antioxidant, produced during the process of red ginseng by Maillard reaction. Acidic-polysaccarides and maltol were increased after the 1st and 3rd steaming and drying treatments, but they were decreased gradually after 5th, 7th, and 9th treatments. Antioxidant activity was increased as increasing treatment times of steaming and drying without significance. Effect of red ginseng extract on inhibition of peroxide was increased gradually until after the 7th treatment, but remarkably decreased after the 9th treatment.

Combinatorial Antitumor Activity of Oxaliplatin with Epigenetic Modifying Agents, 5-Aza-CdR and FK228, in Human Gastric Cancer Cells

  • Park, Jong Kook;Seo, Jung Seon;Lee, Suk Kyeong;Chan, Kenneth K;Kuh, Hyo-Jeong
    • Biomolecules & Therapeutics
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    • v.26 no.6
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    • pp.591-598
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    • 2018
  • Epigenetic silencing is considered to be a major mechanism for loss of activity in tumor suppressors. Reversal of epigenetic silencing by using inhibitors of DNA methyltransferase (DNMT) or histone deacetylases (HDACs) such as 5-Aza-CdR and FK228 has shown to enhance cytotoxic activities of several anticancer agents. This study aims to assess the combinatorial effects of genesilencing reversal agents (5-Aza-CdR and FK228) and oxaliplatin in gastric cancer cells, i.e., Epstein-Barr virus (EBV)-negative SNU-638 and EBV-positive SNU-719 cells. The doublet combinatorial treatment of 5-Aza-CdR and FK228 exhibited synergistic effects in both cell lines, and this was further corroborated by Zta expression induction in SNU-719 cells. Three drug combinations as 5-Aza-CdR/FK228 followed by oxaliplatin, however, resulted in antagonistic effects in both cell lines. Simultaneous treatment with FK228 and oxaliplatin induced synergistic and additive effects in SNU-638 and SNU-719 cells, respectively. Three drug combinations as 5-Aza-CdR prior to FK228/oxaliplatin, however, again resulted in antagonistic effects in both cell lines. This work demonstrated that efficacy of doublet synergistic combination using DNMT or HDACs inhibitors can be compromised by adding the third drug in pre- or post-treatment approach in gastric cancer cells. This implies that the development of clinical trial protocols for triplet combinations using gene-silencing reversal agents should be carefully evaluated in light of their potential antagonistic effects.

Cordyceps militaris Enhances MHC-restricted Antigen Presentation via the Induced Expression of MHC Molecules and Production of Cytokines

  • Shin, Seulmee;Park, Yoonhee;Kim, Seulah;Oh, Hee-Eun;Ko, Young-Wook;Han, Shinha;Lee, Seungjeong;Lee, Chong-Kil;Cho, Kyunghae;Kim, Kyungjae
    • IMMUNE NETWORK
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    • v.10 no.4
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    • pp.135-143
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    • 2010
  • Background: Cordyceps militarys water extract (CME) has been reported to exert antitumor and immunomodulatory activities in vivo and in vitro. However, the therapeutic mechanism has not yet been elucidated. In this study, we examined the effects of CME on the antigen presenting function of antigen presenting cells (APCs). Methods: Dendritic cells (DCs) were cultured in the presence of CME, and then allowed to phagocytose microspheres containing ovalbumin (OVA). After washing and fixing the efficacy of OVA, peptide presentation by DCs were evaluated using CD8 and CD4 T cells. Also, we confirmed the protein levels of proinflammatory cytokines through western blot analysis. Results: CME enhanced both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the expression of both MHC class I and II molecules was enhanced, but there was no changes in the phagocytic activity of exogenous OVA. Furthermore, CME induced the protein levels of iNOS, COX-2, proinflammatory cytokines, and nuclear p65 in a concentration-dependent manner, as determined by western blot. Conclusion: These results provide an understanding of the mechanism of the immuno-enhancing activity of CME on the induction of MHC-restricted antigen presentation in relation to their actions on APCs.

Potential Anticancer Medicinal Plants -A Statistical Evaluation of Their Frequencies of Appearance in Oriental Medicine Formularies- (항암 및 항세균 생약의 통계학적 연구)

  • Cha, Sung-Man
    • Korean Journal of Pharmacognosy
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    • v.8 no.1
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    • pp.1-15
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    • 1977
  • In an attempt to deduce which plants might have been used for their anticancer activities in traditional oriental herb medicine, 127 prescriptions were selected from 'Dong-Eui-Bo-Gam', the Classic Handbook of Korean Traditional Medicine, written by $H_{UH}$ Jun and published in 1613. These are the prescriptions indicated for the systemic treatment of various tumors and some conditions resembling tumors, e.g. inflammatory masses and indurations, and they include 150 natural products of plant origin. The frequency of appearance of each medicinal plant in these selected prescriptions was compared with the frequency of its appearance in all prescriptions listed in 'Bang-Yak-Hap-Pyon', another popular Oriental Medicine Formulary in Korea, written by $H_{WANG}\;Pil-Su$ in 1885. From the latter book, $H_{ONG}$ has recently enumerated frequencies of 235 medicinal plants included in a total of 467 prescriptions. Chi-square tests revealed that 11 plant remedies appear with significantly higher frequency in the prescriptions for "tumors", and 10 for "inflammations". The plants with potential antitumor activities, in decreasing order of statistical significance, are Scirpus maritimus, Curcuma zedoaria, Prunus persica, Rheum coreanum, Foeniculum vulgare, Rhus vernifera, Daphne pseudogenkwa, Galarhaeus sieboldiana, Croton tiglium, Raphanus sativus and Galarhaeus pekinensis. The drugs for potential antibacterial or anti-inflammatory activities are Olibanum(Frankincense), Forsythia coreana, Lonicera japonica, Gleditchia officinalis, $M_{YRRH}$, Trichosanhes kirilowii, Astragalus membranaceus, Rheum coreanum, Platycodon grandiflorum and Fritillaria verticillata. Despite the uncertainties involved in the terminology of various diseases used in pre-modern medicine, and the reservations about the efficacy of remedies used for those diseases, it would be worthwhile to investigate these few selected plants for anticancer, antibacterial, anti-inflammatory or antifungal effects, employing modern scientific methodology.

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Gold nanoparticles enhance anti-tumor effect of radiotherapy to hypoxic tumor

  • Kim, Mi Sun;Lee, Eun-Jung;Kim, Jae-Won;Chung, Ui Seok;Koh, Won-Gun;Keum, Ki Chang;Koom, Woong Sub
    • Radiation Oncology Journal
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    • v.34 no.3
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    • pp.230-238
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    • 2016
  • Purpose: Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. Materials and Methods: Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. Results: Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. Conclusion: In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors.

Inhibition of Tumor Growth in Vitro by a Combination of Extracts from Rosa Roxburghii Tratt and Fagopyrum Cymosum

  • Liu, Wei;Li, Su-Yi;Huang, Xin-En;Cui, Jiu-Jie;Zhao, Ting;Zhang, Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2409-2414
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    • 2012
  • Objective: Traditional Chinese herbal medicines have a very long history. Rosa roxburghii Tratt and Fagopyrum cymosum are two examples of plants which are reputed to have benefits in improving immune responses, enhancing digestive ability and demonstrating anti-aging effects. Some evidence indicates that herbal medicine soups containing extracts from the two in combination have efficacy in treating malignant tumors. However, the underlying mechanisms are far from well understood. The present study was therefore undertaken to evaluate anticancer effects and explore molecular mechanisms in vitro. Methods: Proliferation and apoptosis were assessed with three carcinoma cell lines (human esophageal squamous carcinoma CaEs-17, human gastric carcinoma SGC-7901 and pulmonary carcinoma A549) by MTT assay and flow cytometry, respectively, after exposure to extract from Rosa roxburghii Tratt (CL) and extract from Fagopyrum cymosum (FR). $IC_{30}$ of CL and FR were obtained by MTT assay. Tumor cells were divided into four groups : control with no exposure to CL or FR; CL with $IC_{30}$ CL; FR with $IC_{30}$ FR; CL+FR group with 1/2 ($IC_{30}$ CL + $IC_{30}$ FR). RT-PCR and Western blot analysis were used to detect the expression of Ki-67, Bax and Bcl-2 at mRNA and protein levels. Results: Compared with the CL or FR groups, the combination of CL+FR showed significant inhibition of cell growth and increase in apoptosis; the mRNA and protein expression levels of Ki-67 and Bcl-2 in CL+FR group were all greatly decreased, while the expression of Bax was markedly increased. Conclusions: These results indicate that the synergistic antitumor effects of combination of CL and FR are related to inhibition of proliferation and induction of apoptosis.

Antineoplastic Activity of Crude Saponin Mixture from the Roots of Luffa tuberosa (Roxb.) in Ehrlich Ascites Carcinoma Bearing Mice

  • Yeligar Veerendra C.;K. Murugesh;Dash Deepak;Nayak Siva S.;Maiti Bhim C.;Maity Tapan K.
    • Natural Product Sciences
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    • v.12 no.4
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    • pp.247-253
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    • 2006
  • The antitumor activity of crude saponin mixture obtained from Luffa tuberosa (Roxb.) (Fam; Cucurbitaceae) hairy roots (CSLT) in mice transplanted with Ehrlich ascites carcinoma (EAC) was investigated. The EAC-bearing mice receiving 150 and $300{\mu}g/kg$ body weight, (i.p) of CSLT have shown a dose dependent elevation in tumor-tree survival and a highest number of survivors were observed after administration of CSLT $(300{\mu}g/kg)$, which was considered as an optimum dose for its antineoplastic action. The mean survival time (MST) for this dose was approximately $47.1{\pm}0.74d$, when compared with $19.0{\pm}0.36d$ of untreated control. Administration of $300{\mu}g/kg$ CSLT resulted in 130% long-term increased survival time. The measurement of body weight, tumor volume, packed cell volume, viable and non-viable count indicated the efficacy of CSLT in tumor-bearing mice, there was a significant recovery in hematological profiles, and there was depletion in lipid peroxidation levels, and the antioxidant enzyme activities such as GSH, SOD and CAT were restored to near the normal levels. The CSLT was found to be devoid of conspicuous short-term toxicity in the mice when animals were intraperitoneally injected with 250, 500, 750 and $1000{\mu}g/kg$ bodyweight. The treated mice showed conspicuous toxic symptoms only at a dose of $1500{\mu}g/kg$. Mortality of the animals was monitored up to 14 d post drug treatment, $1/7^{th}$ of the $LD_{50}$ dose has been considered for the optimal antineoplastic activity.

Effect of Resveratrol on Oral Cancer Cell Invasion Induced by Lysophosphatidic Acid

  • Kim, Jin Young;Cho, Kyung Hwa;Lee, Hoi Young
    • Journal of dental hygiene science
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    • v.18 no.3
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    • pp.188-193
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    • 2018
  • The aim of the current study was to demonstrate the potential therapeutic efficacy of resveratrol in oral cancer patients. Lysophosphatidic acid (LPA) intensifies cancer cell invasion and metastasis, whereas resveratrol, a natural polyphenolic compound, possesses antitumor activity, suppressing cell proliferation and progression in various cancer cell lines (ovarian, gastric, oral, pancreatic, colon, and prostate cancer cells). In addition, resveratrol has been identified as an inhibitor of LPA-induced proteolytic enzyme expression and ovarian cancer invasion. Furthermore, resveratrol was shown to inhibit oral cancer cell invasion by downregulating hypoxia-inducible factor $1{\alpha}$ and vascular endothelial growth factor expression. Recently, we demonstrated that LPA is important for the expression of transcription factors TWIST and SLUG during epithelial-mesenchymal transition (EMT) in oral squamous carcinoma cells. In this study, we treated serum-starved cultures of oral squamous carcinoma cell line YD-10B with resveratrol for 24 hours prior to stimulation with LPA. To identify an optimal resveratrol concentration that does not induce apoptosis in oral squamous carcinoma cells, we determined the toxicity of resveratrol in YD-10B cells by assessing their viability using the MTT assay. Another assay was performed using Matrigel-coated cell culture inserts to detect oral cancer cell invasion activity. Immunoblotting was applied for analyzing protein expression of SLUG, TWIST1, E-cadherin, and GAPDH. We demonstrated that resveratrol efficiently inhibited LPA-induced oral cancer cell EMT and invasion by downregulating SLUG and TWIST1 expression. Therefore, resveratrol may potentially reduce oral squamous carcinoma cell invasion and metastasis in oral cancer patients, improving their survival outcomes. In summary, we identified new targets for the development of therapies against oral cancer progression and characterized the therapeutic potential of resveratrol for the treatment of oral cancer patients.

Analgesic Effects of Intrathecal Curcumin in the Rat Formalin Test

  • Han, Yong-Ku;Lee, Seong-Heon;Jeong, Hye-Jin;Kim, Min-Sun;Yoon, Myung-Ha;Kim, Woong-Mo
    • The Korean Journal of Pain
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    • v.25 no.1
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    • pp.1-6
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    • 2012
  • Background: Curcumin has been reported to have anti-inflammatory, antioxidant, antiviral, antifungal, antitumor, and antinociceptive activity when administered systemically. We investigated the analgesic efficacy of intrathecal curcumin in a rat model of inflammatory pain. Methods: Male Sprague Dawley rats were prepared for intrathecal catheterization. Pain was evoked by injection of formalin solution (5%, $50{\mu}l$) into the hind paw. Curcumin doses of 62.5, 125, 250, and $500{\mu}g$were delivered through an intrathecal catheter to examine the flinching responses. The $ED_{50}$ values (half-maximal effective dose) with 95% confidence intervals of curcumin for both phases of the formalin test were calculated from the dose-response lines fitted by least-squares linear regression on a log scale. Results: In rats with intrathecal administration of curcumin, the flinching responses were significantly decreased in both phases. The slope of the regression line was significantly different from zero only in phase 2, and the $ED_{50}$ value (95% confidence interval) of curcumin was $511.4{\mu}g$ (23.5-1126.5). There was no apparent abnormal behavior following the administration of curcumin. Conclusions: Intrathecal administration of curcumin decreased inflammatory pain in rats, and further investigation to elucidate the precise mechanism of spinal action of curcumin is warranted.

Development of a Sensitive Analytical Method of Polynemoraline C Using LC-MS/MS and Its Application to a Pharmacokinetic Study in Mice

  • Pang, Minyeong;Lee, Jaehyeok;Jeon, Ji-Hyeon;Song, Im-Sook;Han, Young Taek;Choi, Min-Koo
    • Mass Spectrometry Letters
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    • v.12 no.4
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    • pp.200-205
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    • 2021
  • Polynemoraline C, a pyridocoumarin alkaloid, exhibits anticholinergic, anti-inflammatory, antitumor, and antimicrobial activities. A sensitive analytical method of polynemoraline C in mouse plasma was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Polynemoraline C and 13C-caffeine (internal standard) in mouse plasma were extracted using a liquid-liquid extraction method coupled with ethyl acetate. This extraction method resulted in high and reproducible extraction recovery in the range of 73.49%-77.31% with no interfering peaks around the peak retention time of polynemoraline C and 13C-caffeine. The standard calibration curves for polynemoraline C were linear over the range of 0.5-200 ng/mL with r2 > 0.985. The accuracy, precision, and the stability of the data were within acceptable limits on the FDA guideline. After intravenous and oral administration of polynemoraline C at doses of 5 and 30 mg/kg, respectively, the present method was successfully applied to the pharmacokinetic study of polynemoraline C. Polynemoraline C in mouse plasma showed a multi-exponential elimination pattern with a high volume of distribution values. This compound's absolute oral bioavailability was found to be 17.0%. Polynemoraline C's newly developed LC-MS/MS method can be used for further studies on the efficacy, toxicity, and biopharmaceutics of polynemoraline C, as well as its pharmacokinetic studies.