• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.85-98
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• 2004

Purpose: Cellular uptake of $^{99}mTc$-sestamibi (MIBI) and $^{99}mTc$-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Celluar uptakes of Tc-99m MIBI and TF were measured in erythroleukermia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto $200{\mu}M\;at\;1{\times}10^6\;cells/ml\;at\;37^{\circ}C$. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of $100{\mu}M$ and the maximal increase at $50{\mu}M$ was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over $1{\mu}M$. With a concentration of $200{\mu}M$ verapamil, MIBI and TF uptakes un K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with $10{\mu}M$, but were also decreased with verapamil higher than $10{\mu}M$, resulting 40% and 5% of baseline at $50{\mu}M$. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at $200{\mu}M$. Conclusion: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.

• YAKHAK HOEJI
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• v.42 no.3
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• pp.233-237
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• 1998

Activity-guided fractionation and repeated column chromatography afforded two cytotoxic compounds R-3 and R-4 from the root of Rumex japonicus HOUTT. Compou nds were identified as musizin and emodin, respectively, by the physicochemical and spectral data. Besides R-3 and R-4, two compounds R-1 and R-2, chrysophanol and physcion, respectively, were also isolated. The compound R-3 and R-4 exhibited cytotoxicity against cultured human tumor cell lines, A-549, SK-OV-3, SK-MEL-2, XF498 and HCT15 with $ED_{50}$ values ranging from 2.68 to $10.06{\mu}g/ml$.

• Archives of Pharmacal Research
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• v.29 no.2
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• pp.131-134
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• 2006

A new compound 2 and two known guaiane-type sesquiterpenoids were isolated from the methylene chloride-soluble fraction of the methanolic extract of the fruits of Torilis japonica (Umbelliferae) through repeated silica gel and Sephadex LH-20 column chromatography. Their chemical structures were elucidated as torilin (1), 11-acetoxy-8-angeloyloxy-$1{\beta}$-hydroxy-4-guaien-3-one ($1{\beta}$-hydroxytorilin, 2), and 11-acetoxy-8-angeloyloxy-$1{\alpha}$-hydroxy-4-guaien-3-one ($1{\alpha}$-hydroxytorilin, 3) by spectroscopic analysis. Compounds 1-3 exhibited cytotoxicity against human A549, SK-OV-3, SK-MEL-2, and HCT15 tumor cells.

• Natural Product Sciences
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• v.20 no.2
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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.

• Journal of the Korean Wood Science and Technology
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• v.26 no.3
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• pp.100-107
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• 1998

Methanol extracts of five Berberidaceae species were examined against tissue factor inhibitory and tumour cell growth inhibitory activity. Methanol extracts of Berberis koreana Palibin showed a strong cytotoxicity activity against SK-MEL-2 (Melanoma) tumour cell lines with more than 90% in $25{\mu}g/m\ell$ and against A549 (Lung carcinoma), SK-OV-3 (Ovarian cancer), XF498 (CNS cancer) and HCTl5 (Colon cancer), other Berberidaceae species except B. koreana species have no effect on the tumour cells. Biologically active compound, therefore, was isolated through the activity guided fractionation and purification. The structure was confirmed by NMR. FT-IR and MS to 2-(3,4-dihydroxybenzyl)-ethyl alcohol. It showed cytotoxicity activity against SNU-C4 tumour cell lines with 50.7% in $50{\mu}g/m\ell$. Methanol extracts of 5 Berberidacae species have no effect on the tissue factor inhibitory activity.

• Archives of Pharmacal Research
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• v.22 no.2
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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.

• YAKHAK HOEJI
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• v.41 no.4
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• pp.524-529
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• 1997

Seventy three hydrolysable tannins and related compounds were isolated from seven Euphorbia plants. Among them, 28 compounds including nine gallotannins, eleven ellagitannins and eight related compounds were selected according to the structural similarity. Cytotoxicity of them on the human tumor cell lines including A-549, SK-OV-3, SK-MEL-2, XF-498 and HCT-15 were evaluated by the SRB method in vitro. 3,4,6-Tri-O-galloyl-D-glucose was shown to exhibit most potent cytotoxic effect($4.4{\mu}g/ml).

• Archives of Pharmacal Research
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• v.15 no.4
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• pp.356-359
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• 1992

The activity-oriented fractionation of Psoralea corylifolia led to an isolation of a (+) bakuchio 1 as an activ eprinciple of its antitumoral property in vitro 1 was observed to exhibit a mild cytotoxicity against five kinds of cultured human cancer cell lines, i. e. the A549, SK-OV-3, SK-MEL-2, XF-498 and HCT15. The synthesized 2, 3-epoxide of (+)-bakuchiol 3 showed the similar activity as the (+) bakuchiol 1, whereas the other oxidation derivatives 4 and 5 including the acetyl (+) bakuchiol 2 showed a decreased activity.

• Archives of Pharmacal Research
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• v.17 no.5
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• pp.348-353
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• 1994

The activity fractionation upon the MeOH extract of the root of trichosanthes kirilowii led to the isolation of eight cucurbitane tritepense namely cucurbitacin .betha. (I), isocucurbitacin .betha.(II), cucurbitacin D(III), isocucurbitacin D(IV), 3-epi-isocucurbitacin .betha(V), dihydrocucurbitain .betha. (VI), dihydroisocucurgbitachin .betha. (VII) and dihydrocucurbitacin E (VIII), as active principles. All isolates were shown to exhibit significant cytotoxicity against cultured human tumor cells, including A-549, Sk-OV-3, Sk-MEL-2, XF-498 and HCT 15, with an exceptionally high potency.

• Archives of Pharmacal Research
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• v.24 no.4
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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${\mu}g/ml$.