• Natural Product Sciences
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• v.15 no.3
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• pp.151-155
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• 2009

Phytochemical investigation of the MeOH extract of the aerial parts of Geranium eriostemon resulted in the isolation of one triterpene, three furofuran lignans, one syringic acid and four flavonoids. Their chemical structures were characterized by spectroscopic methods to be oleanolic acid (1), (-)-kobusin (2), (-)-eudesmin (3), (+)-magnolin (4), syringic acid (5), quercetin (6), juglanin (7), juglalin (8), and hyperin (9). All compounds (1 - 9) were isolated for the first time from this plant source and the compounds 2 - 4 were reported first from the genus Geranium. Compounds 4 - 6 exhibited moderate cytotoxicity against four human cancer cell lines in vitro using a SRB bioassay.

• Natural Product Sciences
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• v.15 no.2
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• pp.90-95
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• 2009

Phytochemical investigation of the MeOH extract of the leaves of Nelumbo nucifera resulted in the isolation of five norsesquiterpenes, four flavonoids, two triterpenes and one alkaloid. Their chemical structures were characterized by spectroscopic methods to be (E)-3-hydroxymegastigm-7-en-9-one (1), (3S,5R,6S,7E)- megastigma-7-ene-3,5,6,9-tetrol (2), dendranthemoside B (3), icariside $B_2$ (4), sedumoside $F_1$ (5), luteolin (6), quercetin 3-0-${\beta}$-D-glucuronide (7), quercetin 3-0-${\beta}$-D-glucoside (8), isorhamnetin 3-0-rutinoside (9), alphitolic acid (10), maslinic acid (11), and N-methylasimilobine (12). Norsesquiterpenoids (1-5) and triterpenes (10-11) were isolated for the first time from this plant. Compounds 6 and 10-12 exhibited considerable cytotoxicity against four human cancer cell lines in vitro using a SRB bioassay.

• Bulletin of the Korean Chemical Society
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• v.29 no.2
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• pp.357-362
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• 2008

A method for synthesizing o-carborane substituted tetrahydroisoquinolines containing a polar functional group such as sulfamide, sulfonic, or phosphoric acid on the nitrogen atom of the piperidine ring, starting from arylethylamine, N-(2-arylethyl)sulfamide, N-(2-arylethyl)sulfamic acid or 2-arylethylamidophosphate, is described. In vitro studies showed the desired compounds 10, 15, 19, and 25 synthesized accumulate to high levels in B-16 melanoma cells with low cytotoxicity.

• Archives of Pharmacal Research
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• v.17 no.6
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• pp.452-457
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• 1994

The water soluble long-chain crosslinker, sulfo-succinimidyl-6-[3'-(2-pyridyldithio)-propion-amido]hexanoate (S-LC-SPDP) was used to prepare ricin A chain (RAT) immunotoxins constructed with whole igG and Fab fragments of the anti-common acute lymphoblastic leukemiz antigen (CALLA)monoclonal antibody. In this study, a) S-LC-SPDP modification efficiencies immunoreactivity and cytotoxicity of immunotoxins constructed were examined. IgG-RTA and Fab-RTA immunotoxins were prepared with 67.3% and 57.0% conjugation yields, respectively. These long spacer intemolecular linked immunotoxins were selectively immunoreactive and to antigen K562 cells. Both IgG-RAT and Fab-RAT immunotoxins were 210-and 45-fold more active than intavt RAT in vitro, respectively.

• Natural Product Sciences
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• v.25 no.1
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• pp.72-75
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• 2019

Bioassay-guided fractionation of the roots of Asarum sieboldii led to the isolation of the six compounds methylkakuol (1), sesamin (2), asarinin (3), xanthoxylol (4), and (2E,4E,8Z,10E/Z)-N-(2-methylpropyl) dodeca-2,4,8,10-tetraenamide (5/6). Among the isolates, xanthoxylol (4) exhibited significant cytotoxicity against human breast cancer cells MCF-7 and MDA-MB-231 in vitro with $IC_{50}$ values of 9.15 and $13.95{\mu}M$, respectively.

• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.32-43
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• 2009

Acetaminophen (APAP) overdose is known to cause severe hepatotoxicity mainly through the depletion of glutathione. In this study, we compared the cytotoxic effects of APAP on both a normal murine hepatic cell line, BNL CL.2, and its SV40-transformed cell line, BNL SV A.8. Gene expression profiles for APAP-treated cells were also obtained using microarray and analyzed to identify differences in genes or profiles that may explain the differences of susceptibility to APAP in these cell lines. These two cell lines exhibited different susceptibilities to APAP (0-$5,000{\mu}M$); BNL SV A.8 cells were more susceptible to APAP treatment compared to BNL CL.2 cells. A dose of $625{\mu}M$ APAP, which produced significant differences in cytotoxicity in these cell lines, was tested. Microarray analysis was performed to identify significant differentially expressed genes (DEGs) irrespective of APAP treatment. Genes up-regulated in BNL SV A.8 cells were associated with immune response, defense response, and apoptosis, while down-regulated genes were associated with catalytic activity, cell adhesion and the cytochrome P450 family. Consistent with the cytotoxicity data, no significant DEGs were found in BNL CL.2 cells after treatment with $625{\mu}M$ APAP, while cell cycle arrest and apoptosis-related genes were up-regulated in BNL SV A.8 cells. Based on the significant fold-changes in their expression, a genes were selected and their expressions were confirmed by quantitative real-time RT-PCR; there was a high correlation between them. These results suggest that gene expression profiles may provide a useful method for evaluating drug sensitivity of cell lines and eliciting the underlying molecular mechanism. We further compared the genes identified from our current in vitro studies to the genes previously identified in our lab as regulated by APAP in both C57BL/6 and ICR mice in vivo. We found that a few genes are regulated in a similar pattern both in vivo and in vitro. These genes might be useful to develop as in vitro biomarkers for predicting in vivo hepatotoxicity. Based on our results, we suggest that gene expression profiles may provide useful information for elucidating the underlying molecular mechanisms of drug susceptibility and for evaluating drug sensitivity in vitro for extrapolation to in vivo.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.162-169
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• 2001

Background: Nitric oxide (NO), a cytotoxic molecule is produced in various tissues including tumor cells during interleukin-2 (IL-2) therapy . Lymphokine-activated killer (LAK) cells are induced during IL-2 therapy, and have cytotoxic activity against tumor cells. The current study investigated the effects of NO synthesized in target cells or exposure of target cells to NO on the sensitivity of target cells to LAK cell cytotoxicity. Methods: Cytotoxicity was measured using 4 h chromium release assays. LAK cells which were induced by a 4 day incubation of BALB/c mouse splenocytes with IL-2 (6,000 IU/mL) were employed as effector cells. RD-995 skin tumor cells originated from a C3H/HeN mouse were employed as target cells. NO synthesis in target cells was induced by a 24 h incubation of RD-995 cells with $IFN{\gamma}$ (25 U/mL), TNF (50 U/mL) and IL-1 (20 U/mL). S-nitrosyl acetylpenicillamine (SNAP), an NO donor, was used to expose target cells to NO. $N^G$-monomethyl-L-arginine (MLA) and carboxy-PTIO were added during cytotoxicity assays to inhibit NO synthesis, and to scavenge NO produced by target cells, respectively. Results: Sensitivity of NO-producing RD-995 cells to LAK cell cytotoxicity was decreased by addition of MLA and carboxy-PTIO during cytotoxicity assays. However, the two reagents had no effect on the sensitivity of non-NO-producing RD-995 cells. Pretreatment of RD-995 target cells with SNAP increased the sensitivity in comparison with untreated cells. Conclusions: Sensitivity of target cells to LAK cell cytotoxicity is increased by target cell NO synthesis or exposure to NO. Further studies are needed to evaluate whether these in vitro results have relevance to in vivo phenomena.

• Korean Journal of Pharmacognosy
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• v.38 no.2 s.149
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• pp.181-186
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• 2007

Seven phenolic compounds, scopoletin (1), caffeic acid methyl ester (2), apigenin 7-O-${\alpha}$-L-rhamnosyl-(1${\rightarrow}$6)-O-${\alpha}$-D-glucoside (3), isorhamnetin 7-O-${\alpha}$-D-glucoside (4), isorhamnetin 3-O-${\alpha}$-D-glucoside (5), luteolin (6), and quercetin 3-methyl ether (7) were isolated from the methanol extract of the flowers of S. excelsus. Their structures were established by chemical and spectroscopic methods. The isolated compounds were tested for their cytotoxicity against four human cancer cell lines in vitro using a SRB method. The compounds 4 and 7 showed moderate cytotoxicity with ED$_{50}$ values ranging from 1.59 to 13.14${\mu}$g/ml.

• Archives of Pharmacal Research
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• v.23 no.1
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• pp.42-45
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• 2000

6-Arylamino-7-halo-5,8-quinolinediones (4a-4k, 5a-5b) were tested for in vitro cytotoxicity against human solid tumor cell lines such as A 549 (non-small cell lung). SK-OV-3 (ovarian), SK-MEL-2 (melanoma), HCT-15 (colon) and XF 498 (CNS) by SRB assay. The arylamino-7-chloro-5,8-quinolinediones 4 were also evaluated for cyclin-dependent kinase (CDK2 and CDK4) inhibitory effect. Among them, the 5,8-quinolinediones 4a and 5a with 7-(4-fluorophenyl) amino group were found to be potent cytotoxic against HCT 15, SKOV-3 and XF 498, and the compounds 4f and 4i showed inhibitory activities for the CDK4.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.781-785
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• 2002

A series of pyrazoloxyphenyl benzoyl urea derivatives was designed and synthesized for cytotoxic evaluation as potential antitumor agents. The synthetic compounds were evaluated for in vitro cytotoxicity against five human tumor cell lines, including A-549, SKOV-3, SK-MEL-2, XF-498 and HCT-15. Among others, compound 11 exhibited 50∼100 times greater antitumor activities than the commercial product, Cisplatin.