• 한국발생생물학회지:발생과생식
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• 제23권2호
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• pp.119-128
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• 2019

Melanoma is one of the most aggressive and treatment-resistant malignancies. Antidiabetic drug metformin has been reported to inhibit cell proliferation and metastasis in many cancers, including melanoma. Metformin suppresses the mammalian target of rapamycin (mTOR) and our previous study showed that it also inhibits the activity of extracellular signal-regulated kinase (ERK). Paclitaxel is currently prescribed for treatment of melanoma. However, paclitaxel induced the activation of ERK/mitogen-activated protein kinase (MAPK) pathway, a cell signaling pathway implicated in cell survival and proliferation. Therefore, we reasoned that combined treatment of paclitaxel with metformin could be more effective in the suppression of cell proliferation than treatment of paclitaxel alone. Here, we investigated the combinatory effect of paclitaxel and metformin on the cell survival in SK-MEL-28 melanoma cell line. Our study shows that the combination of paclitaxel and metformin has synergistic effect on cell survival and suppresses the expression of proteins involved in cancer metastasis. These findings suggest that the combination of paclitaxel and metformin can be a possible therapeutic option for treatment of melanoma.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.411-417
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• 1998

The role of phospholipase ($A_2\;PLA_2$) in tumor cell growth was investigated using SK-N-MC human neuroblastoma cells. 4-Bromophenacyl bromide (BPB) and mepacrine (Mep), known $PLA_2$ inhibitors, suppressed growth of the tumor cells in a dose-dependent manner without a significant cytotoxicity. Melittin (Mel), a $PLA_2$ activator, enhanced the cell growth in a concentration-dependent fashion. The growth-enhancing effects of Mel were significantly reversed by the co-treatment with $PLA_2$ inhibitors. In addition, Mel induced intracellular $Ca^{2+}$ release from internal stores like as did serum, a known intracellular $Ca^{2+}$ agonist in the tumor cells. Intracellular $Ca^{2+}$ release induced by these agonists was significantly blocked by $PLA_2$ inhibitors at growth-inhibitory concentrations. Arachidonic acid (AA), a product of the $PLA_2-catalyzed$ reaction, induced cell growth enhancement and intracellular $Ca^{2+}$ release. These effects of AA were significantly blocked by BAPTA/AM, an intracellular $Ca^{2+}$ chelator. Taken together, these results suggest that the modulation of $PLA_2$ activity may be one of the regulatory mechanisms of cell growth in human neuroblastoma cells. Intracellular $Ca^{2+}$ may act as a key mediator in the $PLA_2-induced$ growth regulation.

• 생약학회지
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• 제47권1호
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• pp.1-6
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• 2016

Phytochemical investigation of the twigs of Corylopsis coreana afforded 10 phenolic compounds, bergenin (1), 6'-O-galloylbergenin (2), 3'-O-galloylbergenin (3), (-)-catechin (4), (-)-epicatechin (5), (-)-epicatechin-3-O-galloyl ester (6), 4-methoxy-3,-5-dihydroxybenzoic acid (7), gallic acid (8), 2,4,6-trimethoxyphenol-1-O-${\beta}-\small{D}$-glucopyranoside (9), and 2,4,6-trimethoxyphenol-1-O-${\beta}-\small{D}$-(6-O-galloyl)-glucopyranoside (10). Their structures were characterized by spectroscopic data and identified by comparing these data with those in the literatures. The compounds 3, 9 and 10 were isolated for the first time from this source. All the isolates (1-10) were tested for their cytotoxic activity against A549, SK-OV-3, SK-MEL-2, and HCT15 cell lines in vitro using the SRB bioassay. The compounds 5, 7 and 8 exhibited selective cytotoxic activity against SK-MEL-2 cell line.

• 대한한의학회지
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• 제23권2호
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• pp.211-224
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• 2002

Background and Objective : In order to investigate the effects of Gilgyunglwedok-tang (GRT) on antitumor activity and antimetastatic activity, studies were done experimentally. Materials and Methods : Experimental studies were perfonned for the cytotoxic effect on BALB/c mouse lung fibroblast cells, the proliferating effect of splenic lymphocyte, the expression of CD3e/CD4, CD3e/CD8, and B220 in peripheral blood mononuclear cells (PBMCs), the cytotoxic effect on A549, SK-OV-3, SK-MEL-2, MCF-7 cells, the inhibitory effect on the activity of DNA topoisomerase I, the T/C% in ICR mice bearing S-180, the inhibitory effect of Cell adhesive of A549 Cells and SK-OY-3 Cells to complex extracellular matrix, the inhibitory effect on lung colonies, the change of lung tissue, the antiangiogenic activity, and the effect on MMP-2 and MMP-9 gene expression in the RT1080 cell line. Results and Conclusion : The results were obtained as follows : 1. In the cytotoxic effect on BALB/C mouse lung fibroblast Cell, GHT didn't show the significant cytotoxic effect on BALB/C mouse lung fibroblast cell compared to the control group. 2. In thymidine uptake assay, GHT showed the significant proliferating effect of splenic lymphocyte in proportion to the concentration. 3. In the expression of CD3e/CD4, CD3e/CD8, and B220 in peripheral blood mononuclea cells (PBMCs) of mice, GRT had no significant change to the normal group in CD4. However, GRT showed an increase to the normal group in CD8 and GHT in the only $1\mu\textrm{g}/ml$ category showed an increase to the normal group in B220. 4. In the cytotoxic effect of GRT on A549, SK-OY-3, SK-MEL-2 and MCF-7 cells, there was no significant cytotoxic effect compared to the control group. 5. In the inhibitory effect on the activity of DNA topoisomerase I, GHT in the $10\mu\textrm{g}/ml$ category showed the inhibitory effect on the activity of DNA topoisomerase I in proportion to the concentration. 6. In the T/C% in ICRmice bearing S-180, GHTtreated group showed 123.7% of T/C% compared to the control group. 7. In the inhibitory effect of cell adhesive of A549 Cells and SK-OV-3 Cells to complex extracellular matrix, GRT in the only $100\mu\textrm{g}/ml$ category showed the significant inhibitory effect compared to the control group. 8. In the inhibitory effect on lung colonies, GHT showed the significant inhibitory effect on lung colonies compared to the control group. 9. In the change of lung tissue, GHT showed a significant decrease of lung cancer growth, interalveolar fibrosis and hyaline material compared to the control group. In the development of lymphocyte around lung cancer cells and lung parenchymal, GHT showed the significant inducement efficacy compared to the control group. 10. In CAM assay, the antiangiogenic activity of GHT showed 30%. 11. In the effect on MMP-2 and MMP-9 gene expression in the RT1080 cell line, GHT had no significant inhibitory effect on MMP-2 and MMP-9 gene expression compared to the control group. According to the above results, it could be suggested that GHT has an antitumor activity and antimetastatic activity.

• Natural Product Sciences
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• 제17권1호
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• pp.10-13
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• 2011

As parts of our continuing search for biologically active compounds from medicinal plants, we investigated the constituents of the seeds of Amomum xanthioides and isolated a sesquiterpenoid, a nerolidol derivative from its MeOH extract. The chemical structure was determined by spectroscopic methods, including 1D and 2D NMR to be ($2S^*$,$2'R^*$,$5'S^*$)-2-(5'-ethenyltetrahydro-5'-methylfuran-2'-yl)-6-methylhept-5en-2-ol (1). Compound 1 was isolated for the first time from nature source. Compound 1 exhibited a good cytotoxicity against SK-OV-3 and SK-MEL-2 cells ($IC_{50}$: 16.7 and $8.6\;{\mu}M$, respectively) using a SRB bioassay. In this study, we also determined the absolute configuration of 2 reported in previous paper.

• 대한예방한의학회지
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• 제2권1호
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• pp.13-30
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• 1998

제라니올 (1), 올리비톨 (2), 카나비노이드 (3 과 4)와 5-플로르우라실 (5)을 MTT 정량분석법과 SRB 정량분석법으로 인체 피부흑색종세포에 대하여 성장 억제효과를 평가 하였다. 이들 화합물(1, 2, 3, 4와 5)은 마이크로 몰 농도의 범위에 대하여 억제 활성을 나타내었다. 일반적으로 이들 화합물은 $1{\mu}M\;-\;100{\mu}M$ 농도범위에서는 투여량에 따라 항암활성을 나타내었다. 인체 피부흑색종세포에 대한 이들 화합물의 50 %억제 농도 효과에 대한 비교는 다음과 같은 순서로 항암활성이 감소하였다. MTT 정량분석법 ; OLVTL >CBG > CBD > 5-FU >GRNL, SRB 정량 분석법 ; CBG > OLVTL > CBD > CRNL > 5-FU, 카나비노이드 (3 과 4)와 5-플로르우라실 (5)을 MTT정량분석법과 SRB정량분석법으로 인체정상세포에 대하여 독성효과를 측정하였다. 이들 화합물은 마이크로몰농도의 농도범위에서는 투여량에 따라 세포독성을 보였다. 인체정상세포에 대한 이들 화합물의 50 % 독성효과에 대한 비교는 다음과 같은 순서로 세포독성이 감소하였다. MTT정량분석법과 SRB정량분석법 ; CBD > 5-FU > CBG. 따라서 카나비지놀 (3)은 인체정상세포에 대하여 가장 낮은 세포독성을 나타내었다. 따라서 카나비지놀 (3)은 인체 피부흑색종세포에 대하여 가장 강한 성장억제활성을 보였다.

• Archives of Pharmacal Research
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• 제22권2호
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• pp.225-227
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• 1999

A new acylcic deterpene (1) and a known acyclic diterpene 12(S)-hydroxygeranyleraniol (2) were isolated form the aerial parts of Carpesium divaricatum. The structure of 1 was determined to be (2E, 10E)-1, 12-dihydroxy-18-acetoxy-3,7,15-trimethylhexadeca-2,10,14-triene (1) on the basis of spectroscopic studies. Compounds 1 and 2 exhibited cytotoxicity against cultured human tumor cell lines, A549, SK-OV-3, SK-MEL-2, XF498, and $HCT_{15}$, with $ED_{50}$ values ranging from 4.3-10.2 ${\mu}g/ml$ and 4.1-8.3 ${\mu}g/ml$, respectively.

• Archives of Pharmacal Research
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• 제24권4호
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• pp.312-315
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• 2001

Repeated column chromatographic separation of the $CH_{2}Cl_{2}$ extract of Artemisia stolonofera (Asteraceae) led to the isolation of a triterpene (I), a sesquiterpene (II), two aromatic compounds (III and IV) and a benzoquinone (V). Their structures were determined by spectroscopic means to be simiarenol (I), (1S,7S)-1 $\beta$-hydroxygermacra-4(15),5, 10(14)-triene (II), 3'-methoxy-4'-hydroxy-trans-cinnamaldehyde (III), vanillin(IV) and 2,6-dimethoxy-1,4-benzoquinone (V), respectively. Among these products, compound V showed significant cytotoxicity against five human tumor cell lines in vitro, A549 (non small cell lung adenocarcinoma), SK-OV-3 (ovarian), SK-MEL-2 (skin melanoma), XF498 (CNS) and HCT15 (colon) with ED_{50}$ values ranging from 1.33~4.22${\mu}g/ml$.

• 동의생리병리학회지
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• 제16권2호
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• pp.348-352
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• 2002

This study was carried out to evaluate cytotoxic effects of Atractylodes macrocephala Koidz. (A. macrocephala Koidz.) extract on NIH 3T3 fibloblast. SK-MEL-3 (HBT 69) and KB (ATCC No, OCL 17) cell lines. Disruptions in cell organelles were determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyl-2H-tetrazoliumbromide (MTT) assay. 10.2 mg/ml Concentration of A. macrocephala Koidz. extracts in SK-MEL-3 showed that their susceptibility (sensitivity) to these compounds decreased in the following order ; adriamycin > H₂O > ethyl acetate > ethyl alcohol > chloroform > n-hexane in SK-MEL-3 cell lines ; 5-FU > H₂O > n-hexane > ethyl acetate > ethyl alcohol > chloroform in KB cell lines. In order to develop an antimicrobial agent, A. macrocephala Koidz. was extracted with solvents. The minimal inhibitory concentrations (MICs) of each solvent extract of A. macrocephala Koidz. against microogranisms were also examined. Antimicrobial activities of ampicillin and ketoconazole as references were compared to those of each solvent extract of A. macrocephala Koidz. The antimicrobial activity of the ethyl acetate soluble extract of A. macrocephala Koidz. had growth inhibition activity against S. mutans and P. putida (MICs. 500 ㎍/ml). These results suggest that the ethyl acetate soluble extract of A. macrocephala Koidz. possessed antitumorous and antimicrobial agents

• Natural Product Sciences
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• 제20권2호
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• pp.71-75
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• 2014

Nine triterpenes were isolated from the petroleum ether and MeOH extract of Perilla frutescens var. acuta leaves. Their structures were determined to be arjunic acid (1), maslinic acid (2), oleanolic acid (3), euscaphic acid (4), tormentic acid (5), 3-O-trans-p-coumaroyltormentic acid (6), 28-formyloxy-$3{\beta}$-hydroxy-urs-12-ene (7), ursolic acid (8), and corosolic acid (9) by spectroscopic methods. The compounds 1, 2, 4, 6, and 7 were isolated for the first time from this plant and the Genus Labiatae. The isolated compounds (1-9) were tested for cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) in vitro using a Sulforhodamin B bioassay.