• 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.

• Archives of Pharmacal Research
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• v.17 no.5
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• pp.375-377
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• 1994

Thirteen kinds of naturally occurring or derivatised thiterpenes, reported to have an antitumoral property, were reinvestigated on the basis of their direct cytotoxicity or the inhibitory activity on cell growth against five kinds of cultured human tumor cells, i.e., A-549, SK-OV-3, SK-MEL-2, XF-498 and HCT15, in vitro. Ursonic acid III, betulinic acid VIII, betulonic acid X and glycrrhetinic acid XI were exhibitied a marked inhibition on cell growth.

• Korean Journal of Pharmacognosy
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• v.26 no.1
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• pp.47-50
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• 1995

EtOAc soluble part of MeOH extract of Anemarrhena asphodeloides rhizome was evaluated for the cytotoxicity against the five kinds of human tumor cell lines (A-549, SK-OV-3, SK-MEL-2, XF498 and HCT15) in vitro. Bioassay-guided fractionation of EtOAc soluble part led to the isolation of active compound which was identified as timosaponin A-III showed potent cytotoxic activity, but its genin, sarsasapogenin, did not show cell growth inhibition.

• Journal of Haehwa Medicine
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• v.5 no.2
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• pp.503-507
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• 1997

The cytotoxicity-guided fractionation of the roots of Sophora flavescens (Leguminosae) extracts led to the isolation of fifteen active principles 1~15, responsible for the cytotoxicity against five kinds of cultured human tumor cell lines, i.e., A549(non small cell lung), SK-OV-3(ovary), SK-MEL-2(skin), XF498(central nerve system) and HCT-15(colon), evaluated by SRB method in vitro. Compounds 2~14 were classified as unusual flavonoid occurred exclusively in this species and the proliferation of each examined tumor cells were significantly inhibited during the continuous exposure to compounds 1~15 for 48 hours, respectively.

• Archives of Pharmacal Research
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• v.26 no.7
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• pp.521-525
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• 2003

Phytochemical works on the aerial parts of Aster oharai (Compositae) led to the isolation of a new sesquiterpene hydroperoxide, 7$\alpha$-hydroperoxy-3, 11-eudesmadiene (2) and seven known compounds, teucdiol B (1), $\alpha$-spinasterol (3), oleanolic acid (4), $\alpha$-spinasterol 3-Ο-$\beta$-D-glucopyranoside (5), methyl 3,5-di-Ο-caffeoyl quinate (6), 3,5-di-Ο-caffeoylquinic acid (7), 3,4-di-Ο-caffeoylquinic acid (8). The chemical structures of 1-8 were established by chemical and spectroscopic methods. Compound 2 showed cytotoxicity against cultured human tumor cell lines in vitro, SK-OV-3 (ovarian), SK-MEL-2 (skin melanoma), and HCT15 (colon) with $ED_{50}$ values ranging from 3.86-17.21 $\mu$g/mL.

• 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.

• Archives of Pharmacal Research
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• v.24 no.5
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• pp.385-389
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• 2001

Twelve 4-substituted cyclopenta[c]quinoline derivatives were synthesized and evaluated in vitro cytotoxicity against four human cancer cell lines (HOP62, SK-OV-3, MD-MB-468 and T-47D). The compounds 6c and 6e bearing p-anisidine and pyrrolidine side chain were more active than the others.

• Archives of Pharmacal Research
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• v.27 no.1
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• pp.44-47
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• 2004

Loranthus tanakae Fr. et Sav. (Loranthaceae) is a species of mistletoe, a semiparasitic plant growing on the branches of Quercus and Betula species as host trees. In our ongoing search for bioactive compounds from endemic species in Korea, we have investigated to isolate the chemical constituents responsible for the antitumor effect of the MeOH extract of L. tanakae. The ethyl acetate soluble part of the MeOH extract demonstrated a marginal inhibition on the proliferation of the tumor cell lines such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system), and HCT-15 (colon) in vitro. Thus, the activity-guided isolation procedure upon the ethyl acetate soluble part of the extract has been carried out and finally four flavonoid rhamnopyranosides (1-4) were isolated as active principle. The structures of 1-4 were elucidated by the physicochemical and spectral data as rhamnetin 3-O-$\alpha$-L-rhamnoside (1), quercetin 3-O-$\alpha$-L-rhamnoside (2), rhamnocitrin 3-O-$\alpha$rhamnoside (3), and kaempferol 3-O-$\alpha$-L-rhamnoside (4).

• 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.