• Natural Product Sciences
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• v.12 no.4
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• pp.175-192
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• 2006

Screening for the cytotoxicity from plant origin is the first stage for anti-cancer drug development. A variety of terpenoids with exomethylene, epoxide, allyl, $\alpha,\beta-unsaturated$ carbonyl, acetylenes, and $\alpha-methylene-\gamma-lactone$ induces apoptosis and/or differentiation as well as cytotoxicity through the ROS signal transduction pathways. These are found among monoterpenes, sesquiterpenes, triterpenes, flavonoids, coumarins, diarylheptanoids, and even organosulfuric compounds. The most essential characteristics of natural cytotoxic substances is to possess the strong electrophilicity that is susceptible to nucleophilic biomolecules in the cell. Thiol-reductants and superoxide dismutase can block or delay apoptosis. Thus, ROS and the resulting cellular redox-potential changes can be parts of the signal transduction pathway during apoptosis. Disturbance of the balance of oxireduction by the pigment of natural quinones also caused the induction of the differentiation and apoptosis. Saponins with the cytotoxicity are restricted to their monodesmosides, rather than to bisdesmosides. Those saponins exhibited calcium ion-mediated apoptosis in addition to cytotoxicity whereas they showed also differentiation without extracellular calcium ion. The properties on cytotoxicity, apoptosis, and differentiation were assumed to depend on resultant oxidative stress to the cells. In this review, we describe a spectrum of cytotoxic compounds with various action mechanisms.

• YAKHAK HOEJI
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• v.45 no.3
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• pp.310-319
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• 2001

To compare skin irritation and cytotoxicity of anti-wrinkle agents, we examined skin irritation of six anti-wrinkle agents (ascorbic acid, glycolic acid, all trans-retinoic acid, ginseng extract, retinol, EB) in New Zealand white rabbit. Cytotoxicity of these agents was determined by MTT [tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] at multi-time points in cultured HaCaT cell, a human immortalized keratinocyte cell. We then analyzed correlation between skin irritation and cytotoxicity by spearman's rank correlation analysis. All trans-retinoic acid showed the highest primary irritation index (0.92) in skin irritation test. Being all the six agents not irritant, retinal showed the most cytotoxic agents. The correlation between skin irritation and cytotoxicity ($IC_{50}$/ at different time point was 0.814, 0.757, 0.814 and 0.7 at 3, 24, 48 and 72 h, respectively. We also fecund that IC$_{20}$ and IC$_{80}$ of these agents showed similar correlation with skin irritation. These results therefore demonstrated that there is close correlation between skin irritation and cytotoxicity $IC_{50}$/ value by MTT in HaCaT cell at early time points by anti-wrinkle agents or IC$_{20}$ value. $IC_{50}$/ at earily time point or IC$_{20}$ values may be reliable alternative determinant of skin irritation.n.

• Korean Journal of Microbiology
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• v.36 no.4
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• pp.312-315
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• 2000

Paecilomyces tenuipes DGUM 32001, an entomopathogenic fungus, was examined to evaluate in vitro cytotoxicity against several human cancer cells. The fruiting bodies of P. tenuipes were extracted with methanol and fractioned with some organic solvents i.e. chloroform, ethyl acetate, and butanol. The methanol extracts of P. tenuipes showed significant cytotoxicity against human cancer cell lines; HeLa, HeLa S3, and A-431. Among the fractions tested, the ethyl acetate fraction had the highest cytotoxicity against three cancer cell lines. The $IC_{50}$ values of ethyl acetate fraction against HeLa, HeLa S3, and A-431 were 13, 35, and 30 $\mu$g/ml, respectively. However, cytotoxicity might not be due to apoptosis. The methanol extract of cultured mycelia showed high cytotoxicity against HeLa cell lines.

• YAKHAK HOEJI
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• v.47 no.4
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• pp.230-233
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• 2003

Previously, protoberberine alkaloids such as berberine and palmatine have been found to lower dopamine content in PC12 cells (Shin et at., 2000). In this study, the effects of berberine and palmatine on L-DOPA-induced increase in dopamine level and cytotoxicity in PC12 cells were investigated. Treatment of PC12 with L-DOPA at concentration ranges of 20∼50 $\mu$M increased dopamine content and the increase in dopamine levels by L-DOPA was inhibited by 10∼40 $\mu$M berberine and 10∼80 $\mu$M palmatine, which the concentration ranges did not show a cytotoxicity. However, berberine and palmatine at concentrations higher than 50 $\mu$M and 100 $\mu$M caused a cytotoxicity, respectively. In addition, berberine (10∼20 $\mu$M) and palmatine (10∼50 $\mu$M) at non-cytotoxic concentration ranges aggravated L-DOPA-induced cytotoxicity in PC12 cells (L-DOPA concentration ranges, 20∼50 $\mu$M). The L-DOPA-induced cytotoxicity was also significantly potentiated by berberine (50 $\mu$M) and palmatine (100 $\mu$M) with cytotoxic ranges. These data demonstrate that berberine and palmatine inhibit L-DOPA-induced increase in dopamine content and stimulate L-DOPA-induced neurotoxicity. Therefore, the possibility that the long-term L-DOPA treated patients with berberine and palmatine could be checked the adverse symptoms.

• Journal of Society of Preventive Korean Medicine
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• v.13 no.2
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• pp.1-18
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• 2009

Objectives : In order to evaluate the cytotoxicity of hexavalent chromium, the cytoprotective effect of phenolic compounds against hexavalent chromium-induced cytotoxicity, cell viability, cell adhesion ability, lactate dehydrogenase(LDH) activity, and morphological changes of cells were examined. Methods : We measured the cytotoxicity of hexavalent chromium with 3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium bromide(MTT), 2,3-bis-[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-caboxanilide (XTT), LDH and DPPH methods. Results : The cytotoxicity of hexavalent chromium($IC_{50}$, $44.0-51.0{\mu}M$) was high according to the toxic criteria. Cytoprotective effect of phenolic compounds against $IC_{50}$ value of hexavalent chromium in cell morphology increased in a concentration-dependent manner. Conclusions : These results suggest that 3,4,5-trihydroxybenzoic acid may be used as a cytoprotective agent against chromium(IV)-mediated cytotoxicity.

• Restorative Dentistry and Endodontics
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• v.7 no.1
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• pp.85-99
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• 1981

This study was to evaluate the cytotoxic effect of three root canal disinfectants (formocresol, camphorated phenol and eugenol) and ten root canal sealers(Cavitec, Hypo-cal, Vitapex, AH26, Canals, Mynol, $N_2$, $N_2$-Medical, Z. O. E. and Calvital) in vitro. The experiments were performed in four differrent modes. In the first and second experiment, the "long-distance" cytotoxicity of three root canal disinfectants were tested on L cells. In the third exeriment, ten root canal sealers were tested for cytotoxicity by means of the tissue culture-agar overlay method immediately, 4 and 24 hours after the experiment. In the fourth experiment, the study with radioactively labeled L cells were employed to determine the relative cytotoxicity of ten root canal sealers. The results were as follows; 1. Every vapors from disinfectants showed more or less cytotoxicity. Of the three disinfectats, formocresol appeared to be the highest cytotoxic effect and camphorated phenol was the lowest. 2. Root canal sealers tested in tbis study showed cytotoxicity at every stage of time intervals. 3. The highest cytotoxic effect was freshly mixed $N_2$ meaical and $N_2$ also revealed the highest cytotoxic effect after 4 or 24 hours among these materials. Vitapex was found the lowest cytotoxic effect at all experimental stage. 4. Root canal sealers except N2 and Mynol showed cytotoxic effect were decreased cytotoxicity according to the time elapsed.

• Environmental Mutagens and Carcinogens
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• v.17 no.1
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• pp.7-11
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• 1997

Variations in adriamycin uptake and cytotoxicity were studied in tumor cells that were grown in different growth states and microenvironments. RIF-1 tumor cells were maintained in an RPMI 1640 medium, and grown in either a monolayer or multicell spheroids. For exponentially growing cells, adriamycin cytotoxicity increased with increased dosage up to 2.5 $\mu$g/ml, and this cytotoxicity was reduced when the cells were grown in a plateau phase or in an acidic microenvironment (pH 6.6). This reduced cytotoxicity was correlated with the uptake of the drug. For multicell spheroids, the cytotoxicity of the drug was reduced dramatically, and this reduction was also correlated with a reduced uptake of the drug and an acidic pH inside of the spheroids. When the drug cytotoxicity was evaluated at different locations within the spheroids, the cells in the inner regions were least affected by the drug, suggesting that both an acidic microenvironment and noncycling plateau phase cells are contributing factors in decreasing the efficacy of the drug in an organized tissue, such as multicell spheroids.

• Food Science and Preservation
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• v.8 no.2
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• pp.213-216
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• 2001

Chemoprevetive effect of Saururus Chinensis (Lour.) Bail water extract on several tumor cells and Chinese hamster V79 cells were investigated. The water extracts of Saururus Chinensis (Lour.) Bail showed a higher cytotoxicity effect on the human histiocytic leukemia cells(U937) and protective effects against the cytotoxicity of H$_2$O$_2$. These results suggest that Saururus Chinensis (Lour.) Bail may useful as potential soures of chemopreventive and antioxidative agents.

• The Journal of Korean Academy of Prosthodontics
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• v.40 no.4
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• pp.309-322
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• 2002

The purpose of this study was to investigate the cytotoxicity and mutagenicity of denture base resins. According to manufacturer's instructions, resin specimens were made. Group 1 : heat-polymerizing acrylic resin (Luciton $199^{(R)}$) Group 2 : heat-polymerizing acrylic resin containing polyhedraloligosilsesquioxane(POSS resin) Group 3 : auto-polymerizing acrylic resin (Repair $Acrylic^{(R)}$) Group 4 : direct relining auto-polymerizing acrylic resin (Tokuso $Rebase^{(R)}$). Fresh specimens 24 hrs. and 72 hrs. soaked specimens in distil)ed water were made. Responses with metabolic assay and mutagenesis assay to eluates from resin specimens were measured. Cultures with medium alone provided controls. Cytotoxicity was assessed with agar overlay test. The results were as follows; 1. Group 4 showed higher cytotoxicity than Group 1, Group 2 and Group 3 in fresh, 24-an4 72-hour immersion caries (p<.05). Group 3 showed higher cytotoxicity than Group 2 in fresh cases and showed higher cytotoxicity than Group 1 and Group 2 in 24-and 72-hour immersion cases (p<.05) . Group 1 and Group 2 showed no significant difference. 2. All acrylic denture base resins skewed significant increase of cell activity as immersion time increased (p<.05). 3. Auto-polymerizing acrylic denture base resins skewed higher cytotoxicity than heat-polymerizing acrylic denture base resins (p<.05). 4. All acrylic denture base resins showed lower mutagenicity than controls (p<.05).

• Restorative Dentistry and Endodontics
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• v.21 no.1
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• pp.403-424
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• 1996

Cell culture methods have been used to assess the cytotoxicity of dental materials. Different paramaters are used to monitor cytotoxic effects. But it is difficult to compare each investigator's results with different methods. The objective of this study was to investigate cytotoxic effect of several retrograde filling materials according to cell lines and assay methods. Cytotoxicity of Bestalloy (Dogmyung, Korea), Prisma APH(Densply International Inc., U.S.A.), Clearfil FII (Kuraray Co., Japan), Fuji II (GC Co., Japan), Fuji II LC (GC Co., Japan) and IRM (Densply Co., U.S.A.) on L929, 3T3 and KB permanent cell lines was measured. Radiochromium, Lactate dehydrogenase (LDH) release method and colorimetric assays, namely neutral red (NR) and MTT were used. Each material was mixed according to the manufacturer's instruction. They were tested as solid and extracted state. Cell culture media were added to each mixed or solid materials then the solution was collected and used as extract solutions. Solid Fuji II showed mild cytotoxicity on three cell lines using radiochromium release method. There was no difference in cytotoxicity of extract solution group using radiochromium release method. In colorimetric assay immediate Fuji II group and all the IRM groups showed severe cytotoxic effect. Difference in cyctotoxicity was due to rather kinds of cell lines than assay methods. Solid Fuji II and IRM showed mild cytotoxicity on three cell lines. But extract solutions had different cytotoxic effect according to cell lines using LDH release assay. Light-cured glass ionomer had mild to moderate degree of cytotoxicity on three cell lines. Cytotoxicity was affected by specimen prepaton. Susceptibility of each cell ines were also affected by assay emthods. It was suggested that cytotoxicity study using only one cell line and/or assay method might not accurately reflect the real toxic nature of dental biomaterials.