• Title/Summary/Keyword: Anti-cancer drugs

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Immunostimulating Activity of Beta-Glucan Isolated from the Cell Wall of Mutant Saccharomyces cerevisiae, and Its Anti-Tumor Application in Combination with Cisplatin (Saccharomyces cerevisiae 변이주 세포벽 유래의 베타글루칸의 면역활성 및 Cisplatin과의 병용에 의한 항암 상승작용)

  • Kim, Wan-Jae;Yoon, Taek-Joon;Kim, Dong-Woo;Moon, Won-Kook;Lee, Kwang-Ho
    • The Korean Journal of Food And Nutrition
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    • v.23 no.2
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    • pp.141-146
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    • 2010
  • Cisplatin(cis-diamminedichloroplatium) is one of the most effective anti-cancer drugs being clinically used in the treatment of solid tumors. Despite its therapeutic benefits, its use in clinical practice is often limited because of dose related toxicity. It is known that yeast cell wall beta-glucans possess immuno-modulating properties, which allows for their application in antitumor therapy. IS2 is a kind of beta-glucan derived from the cell wall of mutated Saccharomyces cerevisiae, which exhibits anti-cancer activity in vitro and in vivo. The present study explored the possibility of combination therapy of IS2 with cisplatin. In experimental metastasis of colon26-M3.1 cells, prophylactic intravenous administration of IS-2 in combination with cisplatin effectively inhibited tumor metastasis compared with cisplatin alone or IS-2 treatment in vivo. IS-2 effectively enhanced Th1 type cytokines including IFN-$\gamma$, IL-2, IL-12 and GM-CSF. Simultaneously, this combined treatment inhibited production of Th2 type cytokines compared with control. These results suggested that IS-2 can be applied in combination therapy with anti-cancer drugs to minimize their side effects.

Comparison Study of the Anti-tumor Effects of Hangamjedoktang(Kangaizhidu-tang) with Holotrkhia and Hangamyagjaebang(Kangaiyaocai-fang) (항암제독탕가제조와 항암양제방에 대한 비교연구)

  • 오중환;박종형;한양희;김동우;전찬용;백은기;홍의실;한지완;임영남
    • The Journal of Korean Medicine
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    • v.24 no.3
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    • pp.138-144
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    • 2003
  • Objective : Though modern medicine has made various studies in cancer treatment, the results of the treatments are not satisfactory. Considering this, Oriental medicine can be a breakthrough in treatment of cancer, and therefore, its constant research eagerly needed. According to preceding studies, Hangamjedoktang (Kangaizhidu-tang) with Hagocho appeared to be statistically significant against cancer, and therefore to seek a better medication for cancer, Holotrichia which seemed to be effective against cancer was added to the formula, and herbs which showed an anti-tumor effect in preceding studies composed Hangamyagjaebang. The efficacy of both Hangamjedoktang with Holotrichia (HJJ) and Hangamyagjaebang (Kangaiyaocaijang) (HM) was compared. Methods : To examine the anti-cancer effect of HJJ and HM, inhibitory effect on solid tumor growth in mice induced by Sarcoma-180 (s-180), change of body and organ weight in tumor bearing mice and the activity of machrophages and lymphocytes in the spleen were examined. Results : 1. In the HJJ and HM treated groups, tumor growth was markedly decreased. 2. HJJ and HM increased the activity of ALP which is produced from the splenocytes transplanted with S-180. 3. HJJ and HM increased the ACP activity of the macrophages of the mice transplanted with S-180. Conclusion : These results suggest that HJJ and HM are good candidates for new drugs for cancer therapy.

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Proposal of Dual Inhibitor Targeting ATPase Domains of Topoisomerase II and Heat Shock Protein 90

  • Jun, Kyu-Yeon;Kwon, Youngjoo
    • Biomolecules & Therapeutics
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    • v.24 no.5
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    • pp.453-468
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    • 2016
  • There is a conserved ATPase domain in topoisomerase II (topo II) and heat shock protein 90 (Hsp90) which belong to the GHKL (gyrase, Hsp90, histidine kinase, and MutL) family. The inhibitors that target each of topo II and Hsp90 are intensively studied as anti-cancer drugs since they play very important roles in cell proliferation and survival. Therefore the development of dual targeting anti-cancer drugs for topo II and Hsp90 is suggested to be a promising area. The topo II and Hsp90 inhibitors, known to bind to their ATP binding site, were searched. All the inhibitors investigated were docked to both topo II and Hsp90. Four candidate compounds as possible dual inhibitors were selected by analyzing the molecular docking study. The pharmacophore model of dual inhibitors for topo II and Hsp90 were generated and the design of novel dual inhibitor was proposed.

Mutagenicity of Chinese Herbal Anti-cancer Drugs and Their Antimutagenic Activity to Base-pair Substitution Mutagen (치암중초약의 돌연변이유발 및 돌연변이유발 억제효과)

  • Lee, Hyun-Chul
    • The Journal of the Korean Society for Microbiology
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    • v.22 no.2
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    • pp.185-193
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    • 1987
  • Ten species of herbae, which have been used to treat cancers in Chinese medicine, were tested to investigate their mutagenicity or antimutagenicity in S. typhimurium TA97, TA98, TA100, TA1535, and TA1538. Scolopendra centipede was weakly active in reversion of the frameshift mutation in S. typhimurium TA97 strain and the base-pair substitution in TA100 and TA1535 strains. Other herbae such as Coix lachryma, Dianthus superbus, Tricanthoshse kirilowii, Eupatorium formosanum, Lithospermum erythrorhizon, Ansaema japonicum, Curcuma zedoaria, Helicteres angustifolia, and Euonymus sieboldianus did not show any of the mutagenic potential, regardless of the metabolic activation with rat hepatic microsomal fraction. Dianthus superbus, Eupatorium formosanum, and Euonymus sieboldianus exhibited suppressive activities on microbial mutagenesis of N-methyl-N'-nitrosoguanidine, a base-pair substitution mutagen, in TA1535 and TA100 tester strains. The antimutagenic activities of Dianthus superbus and Euonymus sieboldianus appeared to be dose-dependant.

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Histone Deacetylase-3/CAGE Axis Targets EGFR Signaling and Regulates the Response to Anti-Cancer Drugs

  • Kim, Hyuna;Kim, Youngmi;Goh, Hyeonjung;Jeoung, Dooil
    • Molecules and Cells
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    • v.39 no.3
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    • pp.229-241
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    • 2016
  • We have previously reported the role of miR-326-HDAC3 loop in anti-cancer drug-resistance. CAGE, a cancer/testis antigen, regulates the response to anti-cancer drug-resistance by forming a negative feedback loop with miR-200b. Studies investigating the relationship between CAGE and HDAC3 revealed that HDAC3 negatively regulated the expression of CAGE. ChIP assays demonstrated the binding of HDAC3 to the promoter sequences of CAGE. However, CAGE did not affect the expression of HDAC3. We also found that EGFR signaling regulated the expressions of HDAC3 and CAGE. Anti-cancer drug-resistant cancer cell lines show an increased expression of $pEGFR^{Y845}$. HDAC3 was found to negatively regulate the expression of $pEGFR^{Y845}$. CAGE showed an interaction and co-localization with EGFR. It was seen that miR-326, a negative regulator of HDAC3, regulated the expression of CAGE, $pEGFR^{Y845}$, and the interaction between CAGE and EGFR. miR-326 inhibitor induced the binding of HDAC3 to the promoter sequences in anti-cancer drug-resistant $Malme3M^R$ cells, decreasing the tumorigenic potential of $Malme3M^R$ cells in a manner associated with its effect on the expression of HDAC3, CAGE and $pEGFR^{Y845}$. The down-regulation of HDAC3 enhanced the tumorigenic, angiogenic and invasion potential of the anti-cancer drug-sensitive Malme3M cells in CAGE-dependent manner. Studies revealed that $PKC{\delta}$ was responsible for the increased expression of $pEGFR^{Y845}$ and CAGE in $Malme3M^R$ cells. CAGE showed an interaction with $PKC{\delta}$ in $Malme3M^R$ cells. Our results show that HDAC3-CAGE axis can be employed as a target for overcoming resistance to EGFR inhibitors.

A literature study on cancer therapy of warm-hot oriental medicine (암(癌)의 온열약물(溫熱藥物) 치료법(治療法)에 대(對)한 고찰(考察))

  • Cho, Chin-Ho;Son, Chang-Gyu;Cho, Chong-kwan
    • Journal of Haehwa Medicine
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    • v.9 no.2
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    • pp.223-239
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    • 2001
  • A literature study on cancer therapy of warm-hot oriental medicine was done, and the results were as follows. 1. In oriental medicine, oncogens are six exopathogens, seven modes of emotion, overwork, pathogenic factors, and especially related with pathologic cold situation. 2. There are many capillaries in tuomr, and because temperature of inner space of tumor is higher than normal organization. Tumor cell has a character which is weak for high temperature. 3. Warm-hot herb drugs have effects of dissipating mass, warming kidney to reinforce yang and dispering, so it has a function of suppressing tumor as well as improving immunity in cancer therapy. 4. In traditional medical books, main prescriptions of cancer therapy are xinzhiyinyanggongjiwan(新製陰陽攻積丸), qianjinxiaoshiwan(千金硝石丸), feiqiwan(肥氣丸), xibenwan(息賁丸), fuliangwan(伏梁丸), beiqiwan, bentunwan(賁豚丸), zengsunwujiwan(增損五積丸), and these are composed of warm-hot herb drugs. 5. In current, the study of warm-hot drugs is progressed in immunological capacity, anti-tumor activity, stimulating bone marrow and regulating hormone secretion. It will be expected that advanced study of these must be accomplished in cancer patients.

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Effect of Extracellular Cations on the Cehmotherapeutic Efficacy of Anticancer Drugs

  • Park, Sun-Mi;Han, Sang-Bae;Hong, Dong-Ho;Lee, Chang-Woo;Park, Se-Hyung;Jeon, Young-Jin;Kim, Hwan-Mook
    • Archives of Pharmacal Research
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    • v.23 no.1
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    • pp.59-65
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    • 2000
  • Cancer development and the efficiency of chemotherapy relies on the patients calcium-related pathological status such as hyper- or hypocalcemica. In the present study, we investigated the effect of extracellular cations such as calcium and magnesium on the therapeutic efficacy of antitumor drugs. The analytic parameters used were cellular drug uptake/excretion and the chemosensitivity of the human breast cancer cell lines, MCF7 and MCF7/ADR. Both calcium and magnesium ions decreased the membrane permeability of cancer cells, which was determined bycell size analysis. These divalent ions also lowered the drug uptake and the cytoplasmic levels of rhodamine 123 and adriamycin, suggesting that they might interfere with the diffusion of these drugs by modifying the physical properties of the cytoplasmic membrane. The acute cytotoxicity of adriamycin after a short period of incubation correlated with changes in its cytoplasmic level. Our results indicate that these extracellular cations might play an important role in the therapeutic activities of anticancer drugs in cancer patients. These results also provide insight a new aspect of chemotherapy, because they suggest that the therapeutic dose of anti-cancer drugs should be modified in cancer-bearing patients presenting with abnormal blood calcium levels.

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Inhibitory effect of Rhus verniciflua Stokes extract in MCF-7 human breast cancer cells (참옻 추출물의 MCF-7 인체 유방암 세포에서 증식 억제효과)

  • Kim, Min Sung;An, Won Gun;Lee, Jang Cheon
    • Herbal Formula Science
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    • v.24 no.4
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    • pp.283-288
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    • 2016
  • Objectives : The purpose of this study was to investigate the anti-cancer effects of extract of Rhus verniciflua Stokes (RVS) in human breast cancer cell lines. Methods : In cultured human breast cancer MCF-7 cells, we investigated growth inhibitory effect of RVS. MCF-7 cells were cultured with various concentrations (0, 200, 300, and 400 ug/ml) of RVS at $37^{\circ}C$ for 24 h. We performed CCK-8 assay and flow cytometry for detection of Annexin V-PI staining. Results : As a result, RVS inhibits the cell growth and induction of apoptosis in dose dependent manner in MCF-7 breast cancer cells. Conclusion : RVS has anti-cancer activities and induced apoptosis in human breast cancer MCF-7 cells. Therefore we suggest that RVS can use as a novel class of anti-cancer drugs.

Discovering the anti-cancer phytochemical rutin against breast cancer through the methodical platform based on traditional medicinal knowledge

  • Jungwhoi Lee;Jungsul Lee;WooGwang Sim;Jae-Hoon Kim;Chulhee Choi;Jongwook Jeon
    • BMB Reports
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    • v.56 no.11
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    • pp.594-599
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    • 2023
  • A number of therapeutic drugs have been developed from functional chemicals found in plants. Knowledge of plants used for medicinal purposes has historically been transmitted by word of mouth or through literature. The aim of the present study is to provide a systemic platform for the development of lead compounds against breast cancer based on a traditional medical text. To verify our systematic approach, integrating processes consisted of text mining of traditional medical texts, 3-D virtual docking screening, and in vitro and in vivo experimental validations were demonstrated. Our text analysis system identified rutin as a specific phytochemical traditionally used for cancer treatment. 3-D virtual screening predicted that rutin could block EGFR signaling. Thus, we validated significant anti-cancer effects of rutin against breast cancer cells through blockade of EGFR signaling pathway in vitro. We also demonstrated in vivo anti-cancer effects of rutin using the breast cancer recurrence in vivo models. In summary, our innovative approach might be proper for discovering new phytochemical lead compounds designing for blockade of malignant neoplasm including breast cancer.

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Immunotherapy with methyl gallate, an inhibitor of Treg cell migration, enhances the anti-cancer effect of cisplatin therapy

  • Kim, Hyunseong;Lee, Gihyun;Sohn, Sung-Hwa;Lee, Chanju;Kwak, Jung Won;Bae, Hyunsu
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.3
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    • pp.261-268
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    • 2016
  • $Foxp3^+$ $CD25^+CD4^+$ regulatory T (Treg) cells are crucial for the maintenance of immunological self-tolerance and are abundant in tumors. Most of these cells are chemo-attracted to tumor tissues and suppress anti-tumor responses inside the tumor. Currently, several cancer immunotherapies targeting Treg cells are being clinically tested. Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. While cisplatin is a powerful drug for the treatment of multiple cancers, there are obstacles that limit its use, such as renal dysfunction and the development of cisplatin-resistant cancer cells after its use. To minimize these barriers, combinatorial therapies of cisplatin with other drugs have been developed and have proven to be more effective to treat cancer. In the present study, we evaluated the effect of the combination therapy using methyl gallate with cisplatin in EL4 murine lymphoma bearing C57BL/6 mice. The combinatorial therapy of methyl gallate and cisplatin showed stronger anti-cancer effects than methyl gallate or cisplatin as single treatments. In Treg cell-depleted mice, however, the effect of methyl gallate vanished. It was found that methyl gallate treatment inhibited Treg cell migration into the tumor regardless of cisplatin treatment. Additionally, in both the normal and cisplatin-treated tumor-bearing mice, there was no renal toxicity attributed to methyl gallate treatment. These findings suggest that methyl gallate treatment could be useful as an adjuvant method accompanied with cisplatin therapy.