• Biomolecules & Therapeutics
• /
• v.16 no.2
• /
• pp.87-94
• /
• 2008

In view of obtaining potential anticancer compounds, we studied the inhibitory activity and the cytotoxic effects of a candidate compound in cancer cells. The cytotoxic effects of cannabidiol (CBD) in vitro were evaluated in NIH3T3 fibroblasts, B16 melanoma cells, A549 lung cancer cells, MDA-MB-231 breast cancer cells, Lenca kidney cells and SNU-C4 colon cancer cells. The cells were cultured in various concentrations of CBD for 48 h and 25 ${\mu}$M of CBD for 6-36 h. The cells were observed to exhibit inhibitory effects of the cell viability in their growth, and then cytotoxicity was estimated. The inhibitory activity of CBD was increased in all cancer cells and showed especially strong increment in breast cancer cells. The cytotoxicity of CBD increased in a dose- and time-dependent manner with growth inhibition in all cancer cell lines. Also, to assess the membrane toxicity induced by CBD, we investigated lactate dehydrogenase (LDH) release. After treatment with various concentrations of CBD, LDH release rate of cancer cells was accelerated. On the other hand, in the induction of cell death, caspase-3, -8 and -9 activations were detected in cancer cells after treatment with various concentrations of CBD, and CBD effectively induced activity of caspase-3, -8 and -9 in A549 lung cancer cells, MDAMB-231 breast cancer cells and Renca kidney cells. Therefore these results suggest that CBD has a possibility of anticancer agents and anticancer effects against cancer cells by modulation of apoptotic pathway in the range of 5-80 ${\mu}$M concentration.

• Journal of the Korean Wood Science and Technology
• /
• v.46 no.2
• /
• pp.166-177
• /
• 2018

Plant essential oils are defined as fragrant volatile oils extracted from leaves, stems, fruits, flowers, and roots of a plant. Such oils are composed of multiple components and multiple functions. By accumulation of inductive information, various plant essential oils have been studied for using in therapeutic medicine for various diseases. Despite of the apparent advantages of essential oils as a source of therapeutic medicines, plant essential oils have many limitations, including cytotoxic side effects. Therefore, it is necessary to evaluate the toxicity and the mechanisms of cytotoxicity of such oils. In this study, we evaluated the cytotoxicity to human-derived cell lines of 10 plant essential oils provided by National Institute of Forest Science (i.e., Larix kaempferi; Abies holophylla; Zanthoxylum ailanthoides; Pinus parviflora; Tsuga sieboldti; Chamaecyparis pisifera; Cryptomeria japonica; Pinus densiflora; Illicium anisatum; Pinus thunbergii). Cytotoxicity evaluations were accomplished by using CCK-assays and PCR-based cytotoxicity-related marker gene analyses with A549 cell line, and the Detroit551 cell line which are lung and skin cell line. The genes were analyzed included caspase-3 has a role in cell apoptosis, and the other cyclinA, cyclinB, cyclinD, and cyclinE regulated cell cycling for the cell proliferation. By examining the five cytotoxicity-related marker genes by performing real-time PCR and examined the cytostatic gene regulation associated with the various essential oils. The results of this study showed that the degree of cytotoxicity and the cytostatic gene regulation which could give precious information for using the plant essential oil for the clinical usages.

• Journal of Radiation Protection and Research
• /
• v.11 no.1
• /
• pp.44-50
• /
• 1986

Tissue distribution and blood chemistry of uranium in serum levels of BUN, Creatinine, SGPT and SGOT were determined in rats after the administration of uranylnitrate. Determination of uranium in organ was done by radio activation analysis. Radioactivity of $^{239}Np$ in lung was higher than in other tissues (e.g. liver, kidneys, spleen, tibia, testes, stomach and brain). Correlations between BUN and Creatinine were positively increased after the administration of 25 mg/kg uranylnitrate. The SGPT and SGOT activities showed weak correlation with the control group. However, activities of SGPT and SGOT after the administration of lmg/kg uranylnitrate showed high peak at 90 min interval. Uranium uptake by liver and kidneys increased at early period and decreased immediately to the control level. Lung who confirmed to be the critical organ on toxic effect by uranylnitrate.

• Korean Journal of Pharmacognosy
• /
• v.40 no.3
• /
• pp.205-212
• /
• 2009

Antitumor activity of Korean mistletoe extract (KM-110) and European commercial mistletoe preparation (Helixor) was investigated. KM-110 showed the cytotoxic effect that it is high for various tumor cell lines and normal splenocytes in comparison with Helixor. Administration of two mistletoe extracts ($100{\mu}g$) to mice did not show any significant changes on the level of glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvate transaminase (GTP), blood creatinine (CRE) and blood urea nitrogen (BUN) in sera. The culture supernatant of macrophages stimulated with KM-110 inhibited effectively tumor growth whereas Helixor had little effect. Administration of KM-110 or Helixor resulted in a effective inhibition of lung metastasis after the i.v. inoculation of colon 26-M3.1 lung carcinoma, B16-BL6 melanoma and L5178Y-ML25 lymphomas. In all cases, the mice treated with KM-110 showed more effective anti-tumor metastatic activity than the mice of Helixor. These results suggest that Korean mistletoe extracts, KM-110 might be used as an alternative methods having antitumor activity like European mistletoe preparation, Helixor.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.15
• /
• pp.6621-6626
• /
• 2015

Purpose: To evaluate effects of metformin on clinical outcome of non-diabetic patients with stage IV NSCLC. Materials and Methods: A prospective, randomized, open-label, controlled pilot study was conducted on patients with stage IV NSCLC with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2, excluding patients with diabetes and lactic acidosis. Thirty chemo-$na\ddot{i}ve$, non-diabetic patients with stage IV NSCLC were enrolled. Fifteen patients received intravenous gemcitabine/cisplatin regimen alone (arm B) while fifteen patients received the same regimen plus daily oral metformin 500mg (arm A). The effect of metformin on chemotherapy-response rates, survival, and adverse events in these patients was evaluated. Results: Objective response rate (ORR) and median overall survival (OS) in arms A and B were 46.7% versus 13.3% respectively, p=0.109 and 12 months versus 6.5 months, respectively, p=0.119. Median progression free survival (PFS) in arms A and B was 5.5 months versus 5 months, p=0.062. No significant increase in toxicity was observed in arm A versus arm B. Percentage of patients who experienced nausea was significantly lower in arm A versus arm B, at 26.7% versus 66.7% respectively, p=0.028. Conclusions: Metformin administration reduced occurrence of chemotherapy induced-nausea. Non-statistically significant improvements in the ORR or OS were observed. Metformin had no effect on PFS.

• Tuberculosis and Respiratory Diseases
• /
• v.66 no.2
• /
• pp.122-126
• /
• 2009

Despite the improvements in supportive care, early and late hematopoietic stem cell transplantation-related complications still remain a significant cause of morbidity and mortality. Pulmonary complications occur in 40-60% of patients who undergo allogeneic hematopoietic stem cell transplantation. Late-onset noninfectious pulmonary complications can occur months and even years after transplantation. Interstital lung disease has also been reported to be a late post-transplant complication. Exposure to cytotoxic drugs and/or irradiation has been implicated as a cause of pulmonary toxicity including pulmonary fibrosis. We report a case of an 18-year-old female with non-classifiable interstitial pneumonia that manifested eight and a half years after allogeneic hematopoietic stem cell transplantation. The condition worsened rapidly and the patient eventually died.

• Radiation Oncology Journal
• /
• v.30 no.1
• /
• pp.43-48
• /
• 2012

Purpose: To develop the dose volume histogram (DVH) management software which guides the evaluation of radiotherapy (RT) plan of a new case according to the biological consequences of the DVHs from the previously treated patients. Materials and Methods: We determined the radiation pneumonitis (RP) as an biological response parameter in order to develop DVH management software. We retrospectively reviewed the medical records of lung cancer patients treated with curative 3-dimensional conformal radiation therapy (3D-CRT). The biological event was defined as RP of the Radiation Therapy Oncology Group (RTOG) grade III or more. Results: The DVH management software consisted of three parts (pre-existing DVH database, graphical tool, and $Pinnacle^3$ script). The pre-existing DVH data were retrieved from 128 patients. RP events were tagged to the specific DVH data through retrospective review of patients' medical records. The graphical tool was developed to present the complication histogram derived from the preexisting database (DVH and RP) and was implemented into the radiation treatment planning (RTP) system, $Pinnacle^3$ v8.0 (Phillips Healthcare). The software was designed for the pre-existing database to be updated easily by tagging the specific DVH data with the new incidence of RP events at the time of patients' follow-up. Conclusion: We developed the DVH management software as an effective tool to incorporate the phenomenological consequences derived from the pre-existing database in the evaluation of a new RT plan. It can be used not only for lung cancer patients but also for the other disease site with different toxicity parameters.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.19 no.4
• /
• pp.1050-1054
• /
• 2005

Recently, arsenic compounds were considered as novel agents for treatment of acute promyelocytic leukemia and malignant tumors. However, it showed severe toxicity effect on normal tissue at the same time. In this study, to investigate the possible molecular mechanism (s) of arsenic compounds as candidate of anti-cancer drugs, we compared the abilities of two arsenic compounds, tetraarsenic oxide $(AS_4O_6)$ and arsenic trioxide (diarsenic oxide, $As_2O_3$), to induce cell growth inhibition as well as apoptosis induction in A549 human non-small cell lung cancer cells. Both $As_4O_6\;and\;As_2O_3$ treatment declined the cell growth and viability of A549 cells in a concentration-dependent manner, which was associated with induction of G1 arrest of the cell cycle and apoptotic cell death. However, $As_4O_6$ induced growth inhibition and apoptosis in A549 cells at much lower concentrations than $As_2O_3.\;As_4O_6$ down-regulated the levels of anti-apoptotic Bcl-2 protein, however, the levels of Bax, a pro-apoptotic protein, were up-regulated in a dose-dependent manner. In conclusion, $As_4O_6$ might be a new arsenic compound which may induce apoptosis in A549 cells by modulation the Bcl-2 family and deserves further evaluation.

• The Korean Journal of Pesticide Science
• /
• v.15 no.4
• /
• pp.374-382
• /
• 2011

We investigated the mutagenicity of methiozolin, newly developed herbicide, in vitro reverse mutation test using Salmonella typhimurium and Escherichia coli, chromosome aberration test using chinese hamster lung (CHL) cells and in vivo micronucleus test of mice. In the reverse mutation test, the methiozolin did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, Escherichia coli WP2uvrA with and without metabolic activation at $5,000{\mu}g$/plate. In the chromosome aberration test, the results showed no incidence of increased structural and numerical chromosome abberrations at any doses tested (80, 40, $20{\mu}g$/mL). In micronucleous test, the ratio of micronuclei was measured in polychromatic erythrocytes with treated methiozolin for ICR mice. No incidence of increased micronuclei were observed in polychromatic erythrocytes (1,500, 1,000, 500 mg/kg). Based on these results, we concluded that methiozolin has no mutagenic toxicity in vitro and in vivo systems.

• Tuberculosis and Respiratory Diseases
• /
• v.55 no.3
• /
• pp.311-316
• /
• 2003

A 34-year-old man was admitted to our hospital due to fever and cough. He received the combination anti-cancer chemotherapy for testicular tumor, including bleomycin. The chest X-ray showed consolidation and ground glass opacity on the right upper lobe and subpleural areas of other lobes. This condition was initially misdiagnosed as a pneuomonia, but consolidation did not disappear after antibiotics treatment. We performed transbronchial lung biopsy and bleomycin induced pulmonary toxicity was confirmed. The bleomycin induced lung injury is the most common chemotherapeutically induced pulmonary disease. Bleomycin induced Bronchiolitis Obliterans Organizing Pneumonia(BOOP) is less common than interstitial pneumonitis and responds well to corticosteroid treatment.