• Title/Summary/Keyword: anti-cancer agents

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Anti-Cancer Activity of the Leave Extracts of Rodgersia podophylla through β-catenin Proteasomal Degradation in Human Cancer Cells (도깨비부채(Rodgersia podophylla) 잎 추출물의 인간 암세포의 β-catenin 분해 유도 활성)

  • Kim, Ha Na;Kim, Jeong Dong;Son, Ho-Jun;Park, Gwang Hun;Eo, Hyun Ji;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.32 no.5
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    • pp.442-447
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    • 2019
  • In this study, we evaluated the effect of Rodgersia podophylla leave extracts (RPL) on ${\beta}-catenin$ level in human cancer cells. RPL dose-dependently inhibited cell proliferation in SW480, A549, MDA-MB-231, PC-3 and AsPC-1 cells. RPL dramatically decreased ${\beta}-catenin$ protein level in all cancer cells. However, decreased level of ${\beta}-catenin$ mRNA expression was observed in A549 and AsPC-1 cells. In addition, RPL dramatically attenuated cyclin D1 mRNA expression in all cancer cells. MG132 decreased the downregulation of ${\beta}-catenin$ protein level induced by RPL in all cancer cells, while RPL-induced downregulation of ${\beta}-catenin$ was inhibited by the inhibition of $GSK-3{\beta}$ by LiCl in MDA-MB-231 cells. RPL phosphorylated ${\beta}-catenin$ and $GSK-3{\beta}$. In addition, the inhibition of $GSK-3{\beta}$ by LiCl attenuated RPL-induced ${\beta}-catenin$ phosphorylation. Based on these findings, RPL may be a potential candidate for the development of chemopreventive or therapeutic agents for human cancer.

Analysis of Existing Guidelines and Randomized, Controlled, Clinical Trials for Development of [Guideline of Clinical Trial with Herbal Medicinal Product for Lung Cancer] (폐암 한약제제 임상시험 가이드라인 개발을 위한 한약제제 무작위배정 대조군 임상시험 고찰)

  • Han, Gajin;Cho, Minji;Park, Eunjoo;Seong, Sin;Kim, Sungsu;Kim, Kwan-Il;Jung, Hee-Jae;Lee, Beom-Joon;Leem, Jungtae
    • The Journal of Korean Medicine
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    • v.40 no.1
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    • pp.153-173
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    • 2019
  • Objectives: This study aimed to ascertain what should be considered in the "Guideline for Clinical Trials with Herbal Medicinal Products for Lung Cancer" by analyzing the existing guidelines and clinical trials. Methods: The committee searched guidelines and clinical trials about herbal medicine for lung cancer. The searched trials were analyzed in terms of inclusion and exclusion of participants, intervention, comparator, outcomes and trial design. Then, we compared the results of our analysis with the guidelines to identify the issues we will have to consider when making the "Guideline for Clinical Trials with Herbal Medicinal Products for Lung Cancer". Several guidelines for anti-tumor agents and clinical trials with herbal medicine were searched on the national institution homepage. The search terms were as follows: 'lung neoplasm', 'herbal medicine', 'Medicine, Korean traditional', 'Medicine, Chinese Traditional' etc. Results: There was no guideline for clinical trial with herbal medicine for lung cancer. In addition, 7 articles were searched through database searching. All the participants had non-small cell lung cancer. The type of intervention was decoction. Comparators included conventional treatments such as chemotherapy. The outcome measurements used in the studies were quality of life, tumor response, and survival duration, etc. Safety was evaluated by recording adverse events and blood test. Conclusions: Findings were made by reviewing existing guidelines and comparing them with clinical trials for lung cancer and herbal medicinal products. These results will be utilized in the development of "Guideline for Clinical Trials with Herbal Medicinal Products for Lung Cancer".

Effects of YideungJetong-Tang on Peripheral Neuropathy Induced by Taxol and Compression Injury in the Rat Sciatic Nerve (이등제통탕(二藤除痛湯)이 Taxol 처리 및 좌골신경의 압박 손상 후 유발된 랫드의 말초신경병증에 미치는 영향)

  • Jeong, Ho Young;Kim, Chul Jung;Cho, Chung Sik
    • The Journal of Korean Medicine
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    • v.33 no.3
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    • pp.133-146
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    • 2012
  • Background: Most antitumor agents have the side effect of chemotherapy-induced peripheral neuropathy (CIPN). Cancer patients who take antitumor agents suffer from CIPN, but there is no known treatment for it. Unlike the central nerve system, the peripheral nerve can self-repair, and the Schwann cell takes this mechanism. Objectives: In this study, we researched the effect of YideungJetong-Tang (YJT) extract on taxol-induced sciatic nerve damage, through in vitro and in vivo experiments. Also, we studied the effect of YJT extract on neurite recovery and anti-inflammatory effect after compression injury of sciatic nerve in vivo. Methods: Vehicle, taxol and taxol+YJT were respectively applied on sciatic nerve cells of rat in vitro, then the cells were cultured. The sciatic nerve cells and Schwann cells were then observed using Neurofilament 200, Hoechst, ${\beta}$ -tubulin, S-$100{\beta}$, caspase-3 and phospho-Erk1/2. CIPN was induced by taxol into the sciatic nerve of rat in vivo, then YJT extract was taken orally. The axons, Schwann cells and neurites of the DRG sensory nerve were then observed using Neurofilament 200, ${\beta}$-tubulin, Hoechst, S-$100{\beta}$, phospho-Erk1/2 and caspase-3. YJT was taken orally after sciatic nerve compression injury, and the changes in axon of the sciatic nerve, Schwann cells and TNF-${\alpha}$ concentration were observed. Results: The taxol and YJT treated group showed significant effects on Schwann cell recovery, neurite growth and recovery. In vivo, YJT compared with control group showed Schwann cell structural improvement and axons recovering effect after taxol-induced Schwann cell damage. After sciatic nerve compression injury, recovery of distal axon, changes of Schwann cell distribution, and anti-inflammatory response were observed in the YJT. Conclusions: Through this study, we found that after taxol-induced neurite damage of sciatic nerve in vivo and in vitro, YJT had significant effects on sciatic nerve growth and Schwann cell structural improvement. In vivo, YJT improved recovery of distal axons and Schwann cells and had an anti-inflammatory effect.

Analysis of Existing Guidelines and Controlled Clinical Trials for Development of [Guideline of Clinical Trials with Herbal Medicinal Products for Colorectal Cancer] (결장직장암 한약제제 임상시험 가이드라인 개발을 위한 한약제제 대조군 임상시험 고찰)

  • Park, Eunjoo;Seong, Sin;Kim, Sungsu;Kim, Jinsung;Park, Jae-Woo;Ko, Seok-Jae;Han, Gajin
    • The Journal of Korean Medicine
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    • v.40 no.1
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    • pp.124-152
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    • 2019
  • Objectives: This study aimed to ascertain what should be considered in the "Guideline for Clinical Trials with Herbal Medicinal Products for Colorectal Cancer" by analyzing the existing guidelines and clinical trials. Methods: The development committee searched guidelines for herbal medicinal products for colorectal cancer that have already been developed. Then, clinical trials for colorectal cancer using herbal medicine were searched. The searched trials were analyzed in terms of inclusion and exclusion of participants, intervention, comparator, outcomes and trial design. Then, we compared the results of our analysis with the regulations and guidelines of the Ministry of Food and Drug Safety in order to identify the issues we will have to consider when making the "Guideline for Clinical Trials with Herbal Medicinal Products for Colorectal Cancer". Several guidelines for anti-tumor agents and clinical trials with herbal medicinal products were searched on the national institution homepage. In addition, 12 articles were searched using a combination of the following search terms: 'colorectal neoplasms', 'herbal medicine', 'Medicine, Korean traditional', 'Medicine, Chinese Traditional', 'medicine, East Asian medicine', 'medicine, Kampo', etc. Results: The characteristics of participants were various, such as people with medical histories of surgeries or recurrent cancers or who complained of chemotherapy-induced side effects. The types of interventions were also various and included decoctions, powders, intravenous fluids, intraperitoneal injections and gargles. Comparators used included placebos and conventional treatments. The outcome measurements used in the studies were quality of life, symptom score, tumor response, and survival duration, etc. Safety was evaluated by recording adverse events. Conclusions: Findings were made by reviewing existing guidelines and comparing them with clinical trials for colorectal cancer and herbal medicinal products. These results will be utilized in the development of the "Guideline for Clinical Trials with Herbal Medicinal Products for Colorectal Cancer".

THE ANTICANCER EFFECT OF PACLITAXEL($Taxol^{(R)}$) IN ORAL SQUAMOUS CELL CARCINOMA XENOGRAFT (이종 이식된 구강편평세포 암종에서 Paclitaxel ($Taxol^{(R)}$)의 항암 효과)

  • Kim, Ki-Hwan;Kim, Chul-Hwan;Han, Se-Jin;Lee, Jae-Hoon
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.28 no.2
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    • pp.95-110
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    • 2006
  • The treatment for oral and maxillofacial carcinoma with chemotherapeutic agents is evaluated by many effective methods to reduce the tumor mass and cancer cell proliferation. However these chemotherapy have many serious side effects, such as bone marrow suppression, renal toxicity, G-I troubles. Therefore a possible approach to develop a clinically applicable chemotherapeutic agent is to screen anticancer activity of Taxol which is known to have very little side effect and have been used to breast cancer and ovarian carcinoma. Taxol is a new anti-microtubular anti-cancer agent extracted from the bark of the Pacific yew, Taxus brevifolia. Paclitaxel(Taxol) acts by promoting tubulin polymerization and over stabilizing microtubules agianst depolymerization. Despite the constant improvements of methods of the cancer treatment especially chemotherapy, the rate of cancer metastasis and recurrent are not decreased. Thus the investigation of new drug which have very little side effect and a possible clinically application continues to be a high priority. Considering that the Taxol have shown very effective chemotherapeutic agent with relatively low toxicity in many solid tumors, it deserves to evaluate its efficacy in oral squamous cell carcinoma. In this study, to investigate the in-vivo and in-vitro anti-cancer efficacy of Taxol in oral squamous cell carcinoma and lastly, the potency of Paclitaxel in the clinical application for oral cancer was evaluated. In vivo study, after HN22 cell line were xenografted in nude mice, the growth of tumor mass was observed, 3 mg/Kg taxol was injected intraperitoneally into nude mice containing tumor mass. The methods of these study were measurement of total volume of tumor mass, histopathologic study, immunohistochemical study, drug resistance assay, growth curve, MTT assay, flow cytometry, cDNA microarray in vivo and in vitro. The results were obtained as following. 1. The visual inspection of the experimental group showed that the volume of the tumor mass was slightly decreased but no significant difference with control group. 2. Ki-67 index was decreased at weeks 4 in experimental group. 3. Microscopic view of the xenografted tumor mass showed well differentiated squamous cell carcinoma and after Taxol injection, some necrotic tissue was seen weeks 4. 4. The growth curve of the tumor cells were decreased after 1day Taxol treatment. 5. According to the MTT assay, HN22 cell line showed relative drug resistancy above $5\;{\mu}g/ml$ concentrations of Taxol. 6. In drug resistance assay, the decrease of cell counts was seen relatively according to concentration. 7. In Flow cytometry, G2M phase cell arrests were seen in low concentration of the Taxol, while S phase cell arrests were seen in high concentration of the Taxol. 8. Using cDNA microarray technique, variable gene expression of ANGPTL4, TXNRD1, FAS, RRAGA, CTGF, CYCLINEA, P19, DUSP5, CEBPG, BTG1 were detacted in the oral squamous cell carcinoma cell after taxol treatment. In this study paclitaxel is effective against oral squamous cell carcinoma cell lines in vitro, but week effect was observed in vivo. So we need continuous study about anticancer effect of taxol in vivo in oral squamous cell carcinoma.

Anti-invasive Effect of the Solvent-partitioned Fractions from Viticis Fructus in PMA-induced HT-1080 Cells (HT-1080 세포에서 만형자 용매 추출물의 암전이 억제효과)

  • Son, Jaemin;Kim, Hojun;Kong, Chang-Suk;Seo, Youngwan
    • Journal of Life Science
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    • v.28 no.3
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    • pp.293-299
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    • 2018
  • Viticis fructus (fruits of Vitex rotundifolia) is the dried fruit from Vitex rotundifolia; is a traditional medicine for treating inflammation, migraines, chronic bronchitis, headaches, eye pain, and gastrointestinal infections; and demonstrates various bioactivities, including anti-allergic, anti-cancer, and anti-inflammatory effects, which are partly due to its phenolic compound content. This study examines the inhibitory effects of viticis fructus (fruits of Vitex rotundifolia) on MMP-2 and MMP-9 expression using gelatin zymography and RT-PCR in phorbol-12-myristate-13-acetate (PMA)-induced HT-1080 fibro-sarcoma cells. Fruits of Vitex rotundifolia were extracted twice using dichloromethane ($CH_2Cl_2$) and methanol (MeOH). The combined crude extracts ($CH_2Cl_2$ and MeOH) significantly inhibited MMP-2 and MMP-9 activities in gelatin zymography. The combined extracts were fractionated into n-hexane, 85% aqueous methanol (85% aq. MeOH), n-butanol, and water, successively according to polarity. Among all solvent-partitioned fractions, 85% aq. MeOH fractions showed the strongest inhibition on the activation of MMP-2 and MMP-9 in gelatin zymography. In PMA-stimulated HT-1080 cells, the expression levels of MMP-2 and MMP-9 mRNA were also greatly inhibited by the 85% aq. MeOH fraction. These results suggest that viticis fructus can be used as an excellent source for anti-invasive agents.

The Effect of Antibacteria and Antioxidantion Activities from Needle Leaf Tree (침엽수 추출물의 항균.항산화 효과)

  • Zhoh, Choon-Koo;Kim, Kyung-Rae;Kim, Joo-Chan
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.33 no.4
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    • pp.269-273
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    • 2007
  • We studied anti-microbial and anti-oxidant activities of bio-active components in stem of Juniperus chinensis L. and leaf of Abies koreana Wilson. Those plants of needle leaf tree family were reported to contain anti-cancer compounds. The anti-bacterial activity was tested by Broth dilution method against Escherichia coli and Staphylococcus aureus. As results, Juniperus chinensis L. and Abies koreana Wilson extracts showed 17.0% and 8.5% higher anti-bacterial activity than methyl paraben, respectively. The free radical scavenging activity of Juniperus chinensis L. and Abies koreana Wilson extracts showed 45 % and 44 % at 5,000 ppm. We measured polyphenol (catechin equivalent) and flavonoids quantity. The Juniperus chinensis L. extract contained 312 mg/g of polyphenol and 105 mg/g of flavonoids. The Abies koreana Wilson extract contained 280 mg/g of polyphenol and 103.8 mg/g of flavonoids. The cytotoxicity of extracts was measured by neutral red assay. Extracts did not affect the viability of CCK-986sk cells up to a concentration of 1,250 ppm. In conclusion, these data suggest that extracts of needle leaf trees would be usefull as antiseptic agents and anti-oxidants for cosmetic products.

FNC, a Novel Nucleoside Analogue, Blocks Invasion of Aggressive Non-Hodgkin Lymphoma Cell Lines Via Inhibition of the Wnt/β-Catenin Signaling Pathway

  • Zhang, Yan;Wang, Chen-Ping;Ding, Xi-Xi;Wang, Ning;Ma, Fang;Jiang, Jin-Hua;Wang, Qing-Duan;Chang, Jun-Biao
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6829-6835
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    • 2014
  • Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents. FNC, 2'-deoxy-2'-${\beta}$-fluoro-4'-azidocytidine, a novel cytidine analogue, has demonstrated significantly inhibitory effects on proliferation of several non-Hodgkin lymphoma (NHL) cell lines. A previous study indicated that FNC effectively inhibited the growth of Raji and JeKo-1 cells in dose-time dependent effects with $IC_{50}$ values of $0.2{\mu}M$ and $0.097{\mu}M$, respectively. This study was focused on investigating the anti-invasive properties of FNC on NHL cells and its potential mechanisms of action. Cell adhesion and transwell chamber assays were utilized to investigate the anti-invasive effects of FNC on Raji and JeKo-1 cells. Real-time PCR and Western blotting were employed to qualify the expression of ${\beta}$-catenin, the glycogen synthase kinase-3 beta (GSK-$3{\beta}$), E-cadherin vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The results revealed that FNC remarkably inhibited the adhesion, migration and invasion of two human aggressive non-Hodgkin lymphoma cell lines in a dose dependent manner. Furthermore, ${\beta}$-catenin, MMP-2, MMP-9, VEGF mRNA and protein levels were decreased after FNC treatment, while GSK-$3{\beta}$ and E-cadherin increased. Our studies thus provide evidence and a rationale that FNC may offer an effective chemotherapeutic agent by regulating the invasion and metastasis of aggressive non-Hodgkin lymphoma via inhibition of the Wnt/${\beta}$-catenin signaling pathway.

In vitro anti-cancer activity of hydrophobic fractions of Sparassis latifolia extract using AGS, A529, and HepG2 cell lines (꽃송이버섯(Sparassis latifolia) 추출물 소수성 분획의 항암 활성)

  • Choi, Moon-Hee;Han, Hyo-Kyung;Lee, Yong-Jo;Jo, Han-Gyo;Shin, Hyun-Jae
    • Journal of Mushroom
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    • v.12 no.4
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    • pp.304-310
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    • 2014
  • The use of mushrooms has immense potential in many diverse applications. Until now, more than 3,000 species are consumed around the world, and more than 100 have shown promising clinical activity against cancer and other chronic diseases. Sparassis latifolia (formerly S. crispa) is an edible mushroom that harbors ${\beta}$-glucan reported to possess immunostimulatory and anticancer properties. However there have been no reports on the anticancer activity of hydrophobic fractions of S. latifolia. In this study, the anticancer activities of S. latifolia extract and hydrophobic fractions were investigated using AGS (stomach cancer), A529 (lung cancer), and HepG2 (liver cancer) cell lines. In cytotoxicity results of A529 cells, fractions of A2, A3, A4, A6, A7, A8, A9, and A10 in all 12 fractions show low $IC_{50}$ values. For HepG2 cells, A7 fraction results in the lowest $IC_{50}$ value while A7, A8, and A11 fractions show low $IC_{50}$ values in AGS cells. S. latifolia extract lead to low cell viability in cancer cells, compared to positive control of paclitaxel. A compound with molecular weight of 181 were detected using HPLC-MS but not identified yet. As a result, the hydrophobic fractions of S. latifolia EtOH extract would be a possible candidate as natural anticancer agents in the future.

Induction of Apoptosis by Sageretia thea Branch Extracts through Activation of NF-κB Signaling Pathway in Human Colorectal Cancer Cells (상동나무(Sageretia thea) 가지추출물의 대장암세포에서 NF-κB 신호전달 활성화를 통한 세포사멸 유도활성)

  • Kim, Jeong Dong;Park, Su Bin;Eo, Hyun Ji;Park, Gwang Hun;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.33 no.5
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    • pp.428-435
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    • 2020
  • In this study, we evaluated the inhibitory effect against cell growth and potential molecular mechanism of 100% ethanol extracts of branch from Sageretia thea in human colorectal cancer cells, HCT116. Ethanol dose-dependently extracts of STB significantly suppressed the growth of HCT116 cells through apoptosis. STB activated NF-κB signaling pathway through IκB-α proteasomal degradation and inducing p65 accumulation in nucleus. The inhibition of GSK3β by LiCl didn't affect STB mediated degradation IκB-α but STB mediated p65 accumulation in nucleus. In addition, STB phosphorylated GSK3β. Based on these findings, STB may be a potential candidate for the development of anti-cancer agents for human colorectal cancer.