• Radiation Oncology Journal
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• v.32 no.3
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• pp.103-115
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• 2014

To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

• Molecules and Cells
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• v.21 no.3
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• pp.395-400
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• 2006

Glutathione S-transferase P1 (GSTP1) plays an important role in detoxification and the metabolism of xenobiotics. Here we show that GSTP1 also regulates the MEKK1-MKK7 signaling pathway. Over-expression of GSTP1 in HEK293 cells inhibited both ${\Delta}MEKK1$- and etoposide-induced apoptosis, and inhibited procaspase-3 activation and PARP cleavage. MEKK1- induced apoptosis requires both its kinase activity and proteolytic cleavage. ${\Delta}MEKK1$ activity was inhibited by over-expression of GSTP1 in vivo and MEKK1 kinase activity was also inhibited by GSTP1 in vitro when assayed with bacterially-expressed MKK7(KM) protein as substrate. GSTP1 inhibition of etoposide-induced cell apoptosis was mainly due to its ability to suppress MEKK1 kinase activity. The glutathione-conjugating activity of GSTP1 was essential for the above effects. These findings provide insight into the mechanism by which GSTP1 protects cells from genotoxin-induced apoptosis.

• Natural Product Sciences
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• v.10 no.6
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• pp.296-301
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• 2004

Previously, a flavonoid fraction, which consisted mainly of protocatechuic acid, fustin, fisetin, sulfuretin, and butein, here named RCMF $({\underline{R}}VS\;{\underline{c}}hloroform-{\underline{m}}ethanol\;{\underline{f}}raction)$, was prepared from a crude acetone extract of Rhus verniciflua Stokes (RVS) which is traditionally used as a food additive and as an herbal medicine. In this study, we evaluated the effects of RCMF on the antioxidant defense system using embryonic normal hepatic cell line (BNL CL.2) and its SV40-mediated transformed cell line (BNL SV A.8). This study demonstrates that RCMF selectively stimulated the antioxidant defense system of normal cells, as BNL CL.2 cells proved to be more sensitive to RCMF-mediated increases of superoxide dismutase, catalase, glutathione, and glutathione reductase than BNL SV A.8 cells. In particular, RCMF caused a significant increase in the malonaldehyde content of BNL SV A.8 cells, which is believed to be closely associated with cytotoxicity of RCMF and RCMF-mediated growth inhibition. Collectively, our findings suggest that the flavonoid fraction, RCMF, selectively stimulates the antioxidant defense system in normal rather than hepatic tumor cells.

• Journal of Sasang Constitutional Medicine
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• v.20 no.3
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• pp.164-175
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• 2008

1. Objective The purpose of this study is to investigate the anti-aging and anti-oxidant effects of Bopyewon-tang(BPW) in Liver and Lung cell. 2. Methods This experiment was used the tissue of liver and lung cells of 6, 52 and 68 weeks old SD rats. Each age group was again divided into three groups. One group, as normal group, was not-treated cells, another group, as control group, was saline-treated cells, and the last group, as experimental group, was BPW -treated cells. After culture for 48 hours, each groups measured the level of SOD, GSH, MDA and NO in the tissue of liver and lung cells. 3. Results and Conclusion 1. The activity of SOD in liver of in 52 w-BPW group, 68 w-BPW group, and in lung of 68 w-BPW were significantly increased in comparison with those of the normal groups. 2. The levels of NO in liver of in 68 w-BPW group was significantly decreased in comparison with those of the normal groups. 3. The levels of MDA in lung of in 68 w-BPW group was significantly decreased in comparison with those of the normal groups.

• The Journal of Korean Medicine
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• v.23 no.3
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• pp.188-199
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• 2002

Objectives : Banhasasim-tang has been clinically used to treat upper gastric intestinal discomfort. The object of this study is to examine the defense effect of Banhasasim-tang for acute duodenal injury of the mouse. Methods and Materials : Twenty-one rats were divided into 3 groups and treated as follows: the control group was untreated mice. The ADE group was acute duodenal-damage-elicited mice. The BST group was Banhasasim-tang treated mice before acute duodenal damage elicitation. The groups were examined with common morphology, paneth cells in intestinal crypt, absorptive cells and goblet cells in epithelium, cell division in mucose, COX-l as mucosal protector, COX-2 (which appears to play an important role in inflammation), IL-2R-inducing cellular immuno-chainreaction, and the distribution of apoptotic cells. Results : 1. Common morphology: the ADE group was observed with duodenal injury - loss of villi, infiltration of cells concerned to inflammation (lymphocytes, granular leukocytes) to submucosal layer - by hemorrhagic erosions, while the BST group was seen the same as normal in proportion to increasing treatment time before injury. 2. Histochemical change: the ADE group was observed with noticeable decreased distribution of absorptive cells with microvilli, acid mucin secreted goblet cell, neutral mucin secreted goblet cell, paneth cells compared to the normal group. The BST group was seen to have distribution of epithelium cells resembling normal in proportion to increasing treatment time before injury. 3. Imnunohistochemical change: the ADE group showed a change of factors leading to duodenal injury as reduce of cytokinesis, COX-1, increase of COX-2, IL-2R-. In contrast, the BST group tended to reduction of cytokinesis, COX-1, increase of COX-2, IL-2R- in proportion to increasing taking time before injury. 4. Apoptosis change: the ADE group showed increasing apoptosis cells, in contrast to the BST group which was the same as normal in proportion to increasing treatment time before injury. Conclusions : According to the above results, by increasing the defense system of mucosal epithelium, Banhasasim-tang is thought to effectively protect tissue against ulcers resulting from acute duodenal injury.

• Preventive Nutrition and Food Science
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• v.4 no.2
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• pp.107-112
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• 1999

Effect of solvent extracts and juice supernatants from kimchis on the growth of various human cancer cells was studied, comparing with the actions on the normal cells. Inhibitory effect of kimchi extracts on[3H] thymidine incorporation n cancer cells was also investigated. The methanol extract, hexane extract and methanol soluble fraction (MSF) of 3-week fermented kimchi did not have growth inhibitory effect on Ac2F rat normal liver cells at the concentrations of 0.5~2%. However, marked decrease in the growth of AGS human gastric cancer cells was shown by the treatment of those extacts. The juice from the kimchi samples also suppressed the growth of K-562 human leukemia cells and MG-63 human osteosarcoma cells. Especially, the juice of 3-week fermented kimchi exhibited the strong growth inhibitory effect in MG-63 human osteosarcoma cells. At the photomicrographs, growth inhibition and morphological change of the cells treated with kimchi juice were observed. And the solvent extracts of 3-week fermented kimchi suppressed the growth of cancer morethan the extracts or juices from fresh and 6-week fermented kimchi. When AGS human gastric cancer cels were treated with the extracts of 3-week fermented kimchi, [3H] thymidine incorporation in the cells also decreased. These results showed that kimchi extracts and juices had growth inhibitory effects on human osteosarcoma, leukemia and gastric cancer cells, but had no toxicity to the normal cells. We suggest that kimchi might have anticancer effect in part due to inhibition of the growth and DNA synthesis of cancer cells.

• Biomedical Science Letters
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• v.20 no.3
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• pp.147-155
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• 2014

It has well studied that immune cells are strongly related to tumor progression and tumor suppression. To identify the difference of immune cell between tumor bearing mice and normal mice, we examined systemically the immune cell of CT26 tumor bearing mice on 21 days after tumor cell administration. As previously reported, CD4+ and CD8+ T cells population of tumor bearing mice significantly decreased 38% and 30% on day 21 compared to that of normal mice, respectively. All subpopulation of CD4 and CD8+ T cell significantly decreased, except CD49b+ T cell subpopulation. But, myeloid cell population ($CD11b^{high}$ and all Gr-1+ subpopulation) of tumor bearing mice significantly increased on day 21. Especially, all subpopulation of CD11b+Gr-1+ cell of tumor bearing mice significantly increased on day 21. Also, Foxp3+$CD25^{high}$ CD4 T cell (regulatory T cells) population significantly increased on day 21. These results suggest that tumor can induce the decline of T lymphocyte and the expansion of myeloid cells and regulatory T cells, and provide the basic information for the study of tumor immunology.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1637-1642
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• 2015

Background: RhoGTPase-activating proteins (RhoGAPs) regulate RhoGTPases in cells, but whether individual reactive oxygen species (ROS) regulate RhoGAPs is unknown. Our previous published papers have shown that deleted in liver cancer 1 (DLC1) inhibits cancer cell migration by its RhoGAP activity. The present study was designed to explore the role of $H_2O_2$ in regulation of DLC1. Materials and Methods: We treated cells with $H_2O_2$ for 24h and phenotypic changes were analyzed by MTT, RT-PCR, Western blotting, immunofluorescence staining and wound healing assays. Results: $H_2O_2$ downregulated cyclin D1 and cyclin E to inhibit proliferation, and upregulated BAX to induce apoptosis in MCF-7 cells. Compared with non-tumorigenic cells, $H_2O_2$ increased expression of DLC1 and reduced activity of RhoA in cancer cells. Stress fiber production and migration were also suppressed by $H_2O_2$ in MDA-MB-231 cells. Conclusions: Our study suggests that $H_2O_2$ inhibits proliferation through modulation of cell cycle and apoptosis-related genes, and inhibits migration by decreasing stress fibers via DLC1/RhoA signaling.

• Korean Journal of Veterinary Research
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• v.63 no.1
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• pp.2.1-2.7
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• 2023

Fenbendazole (FBZ) is a benzimidazole anthelmintic widely used to treat parasitic infections. The anticancer effect of FBZ has been recently highlighted leading to its consideration as a potential anticancer agent. Although previous studies have demonstrated the effect of FBZ on cancer cells, there is a paucity of studies on the effect of FBZ on lymphoma cells and normal immune cells. Herein, we investigated the effects of FBZ on a mouse lymphoma cell line, EL-4 cells, and spleen cells, using vincristine as a positive control. The cellular metabolic activity of EL-4 cells was decreased by FBZ, but that of the spleen cells was not decreased. Moreover, FBZ reduced the mitochondrial membrane potential and induced reactive oxygen species production in EL-4 cells, but not in spleen cells. FBZ induced G2/M phase arrest and increased the sub G0/G1 phase ratio, indicating apoptosis. Furthermore, compared to the control cells, the reactivity of spleen cells pretreated with FBZ to lipopolysaccharide was maintained. In summary, FBZ is cytotoxic to EL-4 cells, but not to spleen cells. This study provides experimental evidence that FBZ exerts an anticancer effect, and less cytotoxic effects and functional damage to normal spleen cells.

• Toxicological Research
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• v.29 no.1
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• pp.35-42
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• 2013

Quantum dots (QDs) have received considerable attention due to their potential role in photosensitization during photodynamic therapy. Although QDS are attractive nanomaterials due to their novel and unique physicochemical properties, concerns about their toxicity remain. We suggest a combination strategy, CdSe/ZnS QDs together with curcumin, a natural yellow pigment from turmeric, to reduce QD-induced cytotoxicity. The aim of this study was to explore a potentially effective cancer treatment: co-exposure of HL-60 cells and human normal lymphocytes to CdSe/ZnS QDs and curcumin. Cell viability, apoptosis, reactive oxygen species (ROS) generation, and DNA damage induced by QDs and/or curcumin with or without ultraviolet A (UVA) irradiation were evaluated in both HL-60 cells and normal lymphocytes. In HL-60 cells, cell death, apoptosis, ROS generation, and single/double DNA strand breaks induced by QDs were enhanced by treatment with curcumin and UVA irradiation. The protective effects of curcumin on cell viability, apoptosis, and ROS generation were observed in normal lymphocytes, but not leukemia cells. These results demonstrated that treatment with QD combined with curcumin increased cell death in HL-60 cells, which was mediated by ROS generation. However, curcumin acted as an antioxidant in cultured human normal lymphocytes.