• Archives of Pharmacal Research
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• v.19 no.4
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• pp.286-291
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• 1996

Phenolic compounds are prevalent as toxins or environmental pollutants, but they are also widely used as drugs for various purpose including anticancer agent. A novel biphenolic compound, bis(2-hydroxy-3-tert-butyl-5-methylphenyl)methane (GERI-BPO02-A) was isolated from the fermentation broth of Aspergillus fumigatus F93 previously, and it has revealed cytotoxicity against human solid tumor cells. Its effective doses that cause 50% inhibition of cell growth in vitro against non-small cell lung cancer cell A549, ovarian cancer cell SK-OV-3, skin cancer cell SK-MEL-2 and central nerve system cancer cell XF498 were 8.24, 10.60, 8.83, $9.85\mug/ml$ respectively. GERI-BPO02-A has also revealed cytotoxicity against P-glycoproteinexpressed human colon cancer cell HCT15 and its multidrug-resistant subline HCT15/CL02, and its cytotoxicity was not affected by P-glycoprotein. We have also tested cytotoxicities of structurally related compounds of GERI-BPO02-A such as diphenylmethane, 1,1-bis(3,4dimethylphenyl)ethane, 2,2-diphenylpropane, 2-benzylpyridine, 3-benzylpyridine, $4,4^I-di-tert-butylphenyl$, bibenzyl, $2,2^I-dimethylbibenzyl$, cis-stilbene, trans-stilbene, 3-tert-butyl-4-hydroxy-5-methylphenyisulfide, sulfadiazine and sulfisomidine for studying of structure and activity relationship, and from these data we could suppose that hydroxyl group of GERI-BPO02A conducted important role in its cytotoxicity.

• Korean Journal of Veterinary Research
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• v.58 no.3
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• pp.119-124
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• 2018

This study was conducted to compare the hemostatic efficacy of three ferric subsulfate- and chitosan-based styptics as a powder and a gel containing ferric subsulfate and chitosan (FSC-PO and FSC-G, respectively) and a soaked pad containing ferric subsulfate and lidocaine (FSL-SP) using a rat tail bleeding model. The cytotoxicity of the styptics against L-929 mouse fibroblasts was also evaluated using a cell counting kit-8 assay. Four groups of 10 rats each were assigned to the three different styptics and a non-treated control groups. Rat tail tips were transected, after which styptics were applied with pressure. The wounds were observed for hemostasis for 3 min, then irrigated with saline to check for recurrent hemorrhage. L-929 mouse fibroblasts were exposed to extracts of the styptics (100 mg/mL) and their dilutions (1:10, 1:100, and 1:1,000). FSC-PO and FSC-G more effectively controlled initial hemorrhage than FSL-SP (p = 0.033). Additionally, FSC-PO and FSC-G more effectively maintained hemostasis than the control group (p = 0.02 and p < 0.01, respectively). However, all styptics showed enhanced cytotoxicity against L-929 cells in a dose-dependent manner. Therefore, although FSC-PO and FSC-G would be recommended to control hemorrhage, the benefits of styptics must be balanced against the clinical significance of their cytotoxicity.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.6 no.1
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• pp.19-28
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• 2000

In this experiment, we examined the the effect of Laetrile Oil to the immune system and tried to disclose the anti-cancer mechanism of this. The result is listed as below. 1. After per-os, sub-cutaneous and into the peritoneal injection of Laetrile Oil to the SPF mice, the LD50 is above 5000mg/kg at even group. 2. Mean survival days of mice treated with laetril oil, after S-180 cells transplantation into the peritoneal cavity decreases 1.5 days(-6.8%) compared with the Mean survival days of the control group(22days.) 3. Effects of laetril oil on natural killer cell activity at Effector/Target Cell Ratio with 100:1, 50:1, 10:1 into methotrexate-pretreated mice is like this.: Compared with $29.22\pm12.7\%$ Cytotoxicity of the control group, sample group's Cytotoxicity had $38.83{\pm}12.5%$ of meaningful acrease. At 100:1 Effecr/Target Cell Ratio. At 50:1 Effector/Target Cell Ratio, control group has $20.02{\pm}9.6%$ Cytotoxiciy and sample group had $31.53{\pm}13.4%$ Cytotoxicity. At 25:1 Effector/Target Cell Ratio control group has $13.60{\pm}6.6%$ Cytotoxicity and sample group had $20.81{\pm}9.8%$ Cytotoxicity According to the above results, the Laetrile Oil represents nontotoxic to a SPF mice. non-effective to transplantable Sarcoma 180 tumors, and activaion in NK cell activity.

• Archives of Pharmacal Research
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• v.22 no.5
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• pp.459-463
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• 1999

The effects of the hindered and non-hindered water soluble long-chain disulfide bonds on the stability and cytotoxicity of the ricin A chain (RTA) immunotoxin were examined. The RTA immunotoxins were prepared with the Fab fragments of anti-common acute lymphoblastic leukemia antigen (CALLA) monoclonal antibody (Fab-RTA) using sulfosuccinimidyl-6-[(-methyl-(-2-pyridyldithio)toluamido]toluamido]hexanoate (S-LC-SMPT) and sulfosuccinimidyl-6-[3-(2-pyridyldithio-propionamido]hexanoate (S-LC-SPDP). The prepared Fab-RTA immunotoxins were evaluated for their conjugation yield, immunoreactivity, thermal and disulfide bond stability and cytotoxicity. The conjugation yield of the Fab-RTA immunotoxin from the water soluble long chain crosslinking agents, S-LC-SMPT and S-LC-SPDP, were comparable. Both Fab-RTA immunotoxins exhibited a similar immunoreactivity and thermal stability in aqueous solution. However, S-LC-SMPT -mediated Fab-RTA, sterically hindered, showed an enhanced disulfide bond stability in vitro over S-LC-SPDP mediated one. In the cytotoxicity against antigenic cell Daudi, the S-LC-SMPT -mediated RTA immunotoxin maintained a comparable cytotoxicity, compared with S-LC-SPDP mediated Fab-RTA immunotoxin.

• Journal of Radiation Industry
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• v.5 no.1
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• pp.35-39
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• 2011

This study was investigated the effect of tumor cell cytotoxicity of gamma irradiated Chaga mushroom extract (CME). CME was prepared by hot water extraction at $70^{\circ}C$ for 4 hours and lyophilized. $Ten\;mg\;ml^{-1}$ of lyophilized CME powder was dissolved with deionized water and then irradiated at the doses of 10, 50, 100, and 150kGy by cobalt 60 gamma irradiator. The gamma-irradiated and non-irradiated CME were treated into the cancer cell, including human stomach cancer and human colon cancer. Cytotoxicity against the cancer cell was increased in gamma-irradiated CME and antioxidant activity was also increased in gamma-irradiated CME, as irradiation dose increased. Therefore, it was considered that gamma irradiation was effective method for improvement of the cancer cell cytotoxicity and antioxidant activity of Chaga mushroom extract.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3191-3196
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• 2013

Leaf extracts of Cassia alata L (akapulko), traditionally used for treatment of a variety of diseases, were evaluated for their potential antitumor properties in vitro. MTT assays were used to examine the cytotoxic effects of crude extracts on five human cancer cell lines, namely MCF-7, derived from a breast carcinoma, SK-BR-3, another breast carcinoma, T24 a bladder carcinoma, Col 2, a colorectal carcinoma, and A549, a nonsmall cell lung adenocarcinoma. Hexane extracts showed remarkable cytotoxicity against MCF-7, T24, and Col 2 in a dose-dependent manner. This observation was confirmed by morphological investigation using light microscopy. Further bioassay-directed fractionation of the cytotoxic extract led to the isolation of a TLC-pure isolate labeled as f6l. Isolate f6l was further evaluated using MTT assay and morphological and biochemical investigations, which likewise showed selectivity to MCF-7, T24, and Col 2 cells with $IC_{50}$ values of 16, 17, and 17 ${\mu}g/ml$, respectively. Isolate f6l, however, showed no cytotoxicity towards the non-cancer Chinese hamster ovarian cell line (CHO-AA8). Cytochemical investigation using DAPI staining and biochemical investigation using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-a method used to detect DNA fragmentation-together with caspase assay, demonstrated apoptotic cell death. Spectral characterization of isolate f6l revealed that it contained polyunsaturated fatty acid esters. Considering the cytotoxicity profile and its mode of action, f6l might represent a new promising compound with potential for development as an anticancer drug with low or no toxicity to non-cancer cells used in this study.

• Journal of Environmental Health Sciences
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• v.36 no.4
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• pp.271-278
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• 2010

The appearance of Asian Dust (AD) originating from China and Mongolia during spring each year is a meteorological phenomenon periodically observed in extensive regions of East Asia. According to a previous epidemiological study, AD has adverse effects on both human beings and ecosystems. In this study, we collected total suspension particles (TSP) in the AD period and Non-AD (NAD) period. We extracted organic components from TSP using dichloromethane (DCM), and the polyaromatic hydrocarbons (PAHs) were analyzed. The DCM extracts contained PAHs such as benzo(b)fluoranthene, benzo[g,h,i]perylene, benzo(k)fluoranthene, benzo(a)pyrene, and pyrene. No significant difference was observed in cytotoxicity of the DCM extracts from AD versus NAD when tested on the human bronchial epithelial cells, BEAS-2B. e also examined the toxic mechanisms of AD extracts in cultured BEAS-2B cells and RAW264.7 cells, and in BEAS-2B cells observed increased levels of reactive oxygen species (ROS), decreased glutathione (GSH), and induced caspase-3 activity. Increased expression of oxidative stress-related and inflammation- related genes were also observed in BEAS-2B cells, while nitric oxide (NO) levels were increased in RAW264.7 cells. Taken together, the results suggest that in these cultured cells, AD may induce cytotoxicity through oxidative stress and pro-inflammatory signals.

• Parasites, Hosts and Diseases
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• v.50 no.4
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• pp.365-369
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• 2012

Acanthamoeba spp. are single-celled protozoan organisms that are widely distributed in the environment. In this study, to understand functional roles of a mannose-binding protein (MBP), Acanthamoeba castellanii was treated with methyl-alpha-D-mannopyranoside (mannose), and adhesion and cytotoxicity of the amoeba were analyzed. In addition, to understand the association of MBP for amoeba phagocytosis, phagocytosis assay was analyzed using non-pathogenic bacterium, Escherichia coli K12. Amoebae treated with mannose for 20 cycles exhibited larger vacuoles occupying the most area of the amoebic cytoplasm in comparison with the control group amoebae and glucose-treated amoebae. Mannose-selected amoebae exhibited lower levels of binding to Chinese hamster ovary (CHO) cells. Exogenous mannose inhibited >50% inhibition of amoebae (control group) binding to CHO cells. Moreover, exogenous mannose inhibited amoebae (i.e., man-treated) binding to CHO cells by <15%. Mannose-selected amoebae exhibited significantly decreased cytotoxicity to CHO cells compared with the control group amoebae, 25.1% vs 92.1%. In phagocytic assay, mannose-selected amoebae exhibited significant decreases in bacterial uptake in comparison with the control group, 0.019% vs 0.03% (P<0.05). Taken together, it is suggested that mannose-selected A. castellanii trophozoites should be severely damaged and do not well interact with a target cell via a lectin of MBP.

• Journal of Pharmaceutical Investigation
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• v.36 no.4
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• pp.231-237
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• 2006

Hypoxia in solid tumors is known to contribute to intrinsic chemoresistance. Histocultures are in vitro 3 dimensional cultures of tumor tissues and maintain the characteristic microenvironment of human solid tumors in vivo including hypoxia and multicellular structure. In this study, we evaluated the pharmacodynamics of tirapazamine(TPZ), a hypoxia-selective cytotoxin, in human non small cell lung cancer(NSCLC) cells grown as monolayers and histocultures. Antiproliferative activity of TPZ was determined after various conditions of drug exposure, and cell cycle arrest and apoptosis were also measured using flow cytometry. In monolayers, hypoxia selectivity measured by hypoxic/normoxic cytotoxicity ratio was increased with longer exposure. Lower cytotoxicity of TPZ was observed in histocultures compared to monolayers, however, a similar level of cytotoxicity was obtained with longer exposure of 96 hr. TPZ induced $G_2/M$ arrest and apoptosis in both culture conditions, which were greatly enhanced under hypoxic condition. Our data clearly showed the different pharmacodynamics of TPZ in monolayers and histocultures. Antiproliferative activity of TPZ against human solid tumors can be improved with longer drug exposure by exploiting drug delivery systems or by combining angiogenesis inhibitors to maintain drug concentration in tumor tissues.