• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.9
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• pp.1439-1444
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• 2004

Antitumor activities of onion methanol extract (OME) and onion Kimchi methanol extract (OKME) were investigated by using aflatoxin $B_1$-mediated Salmonella typhimurium mutagenicity and the model of cytotoxicity on the cancer cell lines. Their immune activities were also investigated by using mouse spleen cells and macrophage cell lines, respectively. OME and OKME showed the enhanced antimutagenicity in a dose-dependent manner in particular, the activity of OKME was higher than that of OME. OME and OKME decreased over 20% of the proliferation of the A549 (lung cancer cell) and MCF-7 (breast cancer cell) cell lines when compared with the control at 1,000 ${\mu}$g/mL. The proliferation of mouse spleen cells and the NO production in marcrophage cell lines treated OME and OKME were increased in a dose-dependent manner compared with untreated control cells, and their activities of OKME were higher than those of OME.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1499-1506
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• 2016

Background: Crocus sativus and its major constituent crocin are well established to have anti-cancer properties in breast cancer cells (MCF-7). However the role of C. sativus extract (CSE) and crocin on caspase signaling mediated MCF-7 cell death at molecular level is remains unclear. In this study, we tried to unravel role of CSE and crocin on caspase mediated MCF-7 cells death and their in vivo preclinical toxicity profiling and immune stimulatory effect. Materials and Methods: CSE extract was fractionated by HPLC and crocin was isolated and characterized by NMR, IR, and MS. MCF-7 cells were treated with both CSE and crocin and expression of Bcl-2 and Bax was assessed after 24 and 36 hours. Furthermore, caspase 3, caspase 8 and caspase 9 expression was determined by Western blotting after 24 hours of treatment. DNA fragmentation analysis was performed for genotoxicity of CSE and crocin in MCF-7 cells. The in vivo toxicity profile of CSE (300 mg/kg of b.wt) was investigated in normal Swiss albino mice. In addition, peritoneal macrophages were collected from crocin (1, 1.5 and 2 mg/kg body weight) treated mice and analyzed for ex vivo yeast phagocytosis. Results: Immunoblot analysis revealed that there was time dependent decline in anti-apoptotic Bcl-2 with simultaneous upregulation of Bax in CSE and crocin treated MCF-7 cells. Further CSE and crocin treatment downregulated caspase 8 and 9 and cleaved the caspase 3 after 24 hours. Both CSE and crocin elicited considerable DNA damage in MCF-7 cells at each concentration tested. In vivo toxicity profile by histological studies revealed no observable histopathologic differences in the liver, kidney, spleen, lungs and heart in CSE treated and untreated groups. Crocin treatment elicited significant dose and time dependent ex vivo yeast phagocytosis by peritoneal macrophages. Conclusions: Our study delineated involvement of pro-apoptotic and caspase mediated MCF-7 cell death by CSE and crocin at the molecular level accompanied with extensive DNA damage. Further we found that normal swiss albino mice can tolerate the maximum dose of CSE. Crocin enhanced ex vivo macrophage yeast phagocytic ability.

• Food Science and Preservation
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• v.12 no.2
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• pp.173-178
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• 2005

Antitumor activities of methanol extract from onion Kochujang (MEOK) were investigated by using aflatoxin $B_{1}-mediated$ Salmonella typhimurium mutagenicity and the model of cytotoxicity on the cancer cell lines. Their immune activities were also investigated using mouse spleen cells and macrophage cell lines, respectively. MEOK showed the enhanced antimutagenicity in a dose-dependent manner. relative to the control group. MEOK decreased over $20\%$ of the proliferation of the A549(lung cancer cell) and MCF(breast cancer cell) cell lines at $1,000\;{\mu}g/mL$ concentration compared with the control cells. The proliferation of mouse spleen cells and the NO production in marcrophage cell lines treated MEOK were increased in a dose-dependent manner, respectively. The activities were higher than that of the control(no added onion) Kochujang.

• Preventive Nutrition and Food Science
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• v.8 no.4
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• pp.356-364
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• 2003

A methanol extract from seeds of Paeonia lactiflora (Paeoniaceae, peony) was found to possess different antiproliferative activities against four different human cancer cell lines: Hela, MCF-7, HepG2 and HT-29. Furthermore, five different methanol (20, 40, 60, 80 and 100 % MeOH) fractions obtained by fractionation of the methanol extract of the seeds on a Diaion HP-20 column exhibited differential antiproliferative effects against the above four cancer cell lines. Among five fractions, the 60 % MeOH fraction showed relatively lower antiproliferative activity on MCF-7 estrogen-sensitive breast cancer cell than the other cancer cell lines. Systematic separation of 60% the MeOH fraction by silica gel and Sephadex LH-20 columns led to the isolation of four known stilbenes, trans-resveratrol (1), trans-(+)- $\varepsilon$ -viniferin (2), gnetin H (3) and suffruticosol B (4). The four stilbenes (1∼4) exerted differential biphasic effects on cell proliferation of MCF-7 cells in a similar manner as genistein, a soybean isoflavone used as a positive reference, in the concentration range from 1.0 to 200 $\mu$M. Three stilbenes (1 ∼ 3) weakly stimulated the proliferation of MCF -7 cells at doses below 10 JIM. However, strong antiproliferative effects on MCF-7 cell were exerted by extract 1 at a dose of 200 JIM, and by 2 and 3 at doses above 25 $\mu$M. In contrast, 4 inhibited the proliferation of MCF-7 cell at a dose below 25 $\mu$M, but stimulated cell proliferation at concentrations of 50 and 100 $\mu$M. All four stilbenes (1∼4) stimulated the proliferation of ROS 17/2.8 osteoblast-like cells in the range of 10$^{-10}$ ∼10$^{-1}$ $\mu$M. Compound 1 exhibited especially potent proliferative activity, although its activity was weaker than that of genistein. Additionally, three resveratrol oligomers (2∼4) also exhibited concentration-dependently moderate proliferative activity, but less than that of 1. These results suggest that resveratrol, and its dimer and trimers from the seeds of Paeonia lactiflora may act as a phytoestrogen, but in a somewhat different manner from that of genistein.

• Archives of Pharmacal Research
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• v.23 no.1
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• pp.59-65
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• 2000

Cancer development and the efficiency of chemotherapy relies on the patients calcium-related pathological status such as hyper- or hypocalcemica. In the present study, we investigated the effect of extracellular cations such as calcium and magnesium on the therapeutic efficacy of antitumor drugs. The analytic parameters used were cellular drug uptake/excretion and the chemosensitivity of the human breast cancer cell lines, MCF7 and MCF7/ADR. Both calcium and magnesium ions decreased the membrane permeability of cancer cells, which was determined bycell size analysis. These divalent ions also lowered the drug uptake and the cytoplasmic levels of rhodamine 123 and adriamycin, suggesting that they might interfere with the diffusion of these drugs by modifying the physical properties of the cytoplasmic membrane. The acute cytotoxicity of adriamycin after a short period of incubation correlated with changes in its cytoplasmic level. Our results indicate that these extracellular cations might play an important role in the therapeutic activities of anticancer drugs in cancer patients. These results also provide insight a new aspect of chemotherapy, because they suggest that the therapeutic dose of anti-cancer drugs should be modified in cancer-bearing patients presenting with abnormal blood calcium levels.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2637-2641
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• 2013

6,8-Dihydroxy-7-methoxy-1-methyl-azafluorenone (DMMA), a purified compound from Polyalthia cerasoides roots, is cytotoxic to various cancer cell lines. The aims of this study were to demonstrate the type of cancer cell death and the mechanism(s) involved. DMMA inhibited cell growth and induced apoptotic death in human leukemic cells (HL-60, U937, MOLT-4), human breast cancer MDA-MB231 cells and human hepatocellular carcinoma HepG2 cells in a dose dependent manner, with $IC_{50}$ values ranging between 20-55 ${\mu}M$. DMMA also decreased cell viability of human peripheral blood mononuclear cells. The morphology of cancer cells induced by the compound after staining with propidium iodide and examined under a fluorescence microscope was condensed nuclei and apoptotic bodies. Mitochondrial transmembrane potential (MTP) was decreased after 24h exposure in all five types of cancer cells. DMMA-induced caspase-3, -8, and -9 activity was strongly induced in human leukemic HL-60 and MOLT-4 cells, while in U937-, MDA-MB231- and HepG2-treated cells there was partial induction of caspase. In conclusion, DMMA-induced activation of caspase-8 and -9 resulted in execution of apoptotic cell death in human leukemic HL-60 and MOLT-4 cell lines via extrinsic and intrinsic pathways.

• Korean Journal of Plant Resources
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• v.21 no.1
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• pp.96-102
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• 2008

Nelumbo nucifera Gaertn.(family Nymphaeaceae) has been used for summer heat syndrome as home remedy in Japan, China and Korea. Although whole plant parts are edible, root is commonly consumed. It has been reported that rhizome extract showed anti-diabetic and anti-inflammatory effects. However, in spite of usefulness for treatment of various diseases, the effect of Nelumbo nucifera rhizome(NNR) on proliferation, migration and matrix degrading enzymes-matrix metalloproteinsases(MMPs), the expression of which degrades extracellular matrix(ECM) leading to metastasis, has not been fully elucidated. We examined the effect of hot water extract of NNR on the proliferation, migration and secretion of MMP-2 and MMP-9 in rat smooth muscle cells(rSMC), epidermoid cancer cells(A431) and breast cancer cells(MDA-MB-231). The proliferation assay was carried out using MTT assay, the principle of which depends upon the conversion of MTT by mitochondrial dehydrogensases of viable cells to formazan crystals. The effect of NNR on migration of cells was examined using wound healing assay. Our results showed that there was inhibition in the proliferation, migration and expression of MMP-2 and MMP-9 in dose dependent fashion in all the cells used. Thus, we concluded that NNR could be used as traditional medicine in the treatment of various diseases where proliferation, migration and MMPs' expression plays a pathological role like in restenosis and metastasis.

• CELLMED
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• v.1 no.1
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• pp.6.1-6.4
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• 2011

For cancer patients undergoing radiation therapy (RT) or systemic chemotherapy (CHT), cancer-related fatigue (CRF) is a common problem that can negatively impact their quality of life. Guarana (Paullinia cupana) is a plant native to the Amazon basin that has been used as a stimulant since pre-Columbian times. PURPOSE: To evaluate the effectiveness of guarana extract on fatigue in BC patients undergoing either CHT or RT. A total of 137 cancer patients (85% with Breast Cancer) undergoing either CHT (101) or RT (36) were randomized to receive either a placebo or guarana. In all 3 studies, the guarana was given as an unmanipulated dry extract at a dose of 75 mg PO QD in the first two studies or 50 mg PO BID in the third study. Patients were crossed over to the other experimental arm, and we evaluated fatigue with the Chalder Scale in all three studies. Guarana significantly improved the The Chalder Scale Global Scores (- 0.85; 95% CI:-1.31 to -0.40; p = 0.0002); Physical Fatigue Scores (-0.44; 95% CI: - 0.74 to - 0.13; p = 0.005) and Mental Fatigue Scores (-0.93; 95% CI: - 1.14 to - 0.72; p < 0.00001). Guarana did not produce any CTCAE grades 3 or 4 toxicities in any of the studies. Guarana is an effective, cheap and non-toxic alternative for the treatment of fatigue in cancer patients undergoing treatment.

• Journal of Korean Neurosurgical Society
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• v.58 no.3
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• pp.217-224
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• 2015

Objective : To investigate the efficacy and safety of fractionated stereotactic radiosurgery for large brain metastases (BMs). Methods : Between June 2011 and December 2013, a total of 38 large BMs >3.0 cm in 37 patients were treated with fractionated Cyberknife radiosurgery. These patients comprised 16 men (43.2%) and 21 women, with a median age of 60 years (range, 38-75 years). BMs originated from the lung (n=19, 51.4%), the gastrointestinal tract (n=10, 27.0%), the breast (n=5, 13.5%), and other tissues (n=3, 8.1%). The median tumor volume was 17.6 cc (range, 9.4-49.6 cc). For Cyberknife treatment, a median peripheral dose of 35 Gy (range, 30-41 Gy) was delivered in 3 to 5 fractions. Results : With a median follow-up of 10 months (range, 1-37 months), the crude local tumor control (LTC) rate was 86.8% and the estimated LTC rates at 12 and 24 months were 87.0% and 65.2%, respectively. The median overall survival (OS) and progression-free survival (PFS) rates were 16 and 11 months, respectively. The estimated OS and PFS rates at 6, 12, and 18 months were 81.1% and 65.5%, 56.8% and 44.9%, and 40.7% and 25.7%, respectively. Patient performance status and preoperative focal neurologic deficits improved in 20 of 35 (57.1%) and 12 of 17 patients (70.6%), respectively. Radiation necrosis with a toxicity grade of 2 or 3 occurred in 6 lesions (15.8%). Conclusion : These results suggest a promising role of fractionated stereotactic radiosurgery in treating large BMs in terms of both efficacy and safety.

• Journal of Korean Neurosurgical Society
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• v.46 no.6
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• pp.538-544
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• 2009

Objective : Primary treatment of spinal metastasis has been external beam radiotherapy. Recent advance of technology enables radiosurgery to be extended to extracranial lesions. The purpose of this study was to determine the clinical effectiveness and safety of stereotactic radiosurgery using Cyberknife in spinal metastasis. Methods : From June, 2002 to December, 2007, 129 patients with 167 spinal metastases were treated with Cyberknife. Most of the patients (94%) presented with pain and nine patients suffered from motor deficits. Twelve patients were asymptomatic. Fifty-three patients (32%) had previous radiation therapy. Using Cyberknife, 16-39 Gy in 1-5 fractions were delivered to spinal metastatic lesions. Radiation dose was not different regarding the tumor pathology or tumor volume. Results : After six months follow-up, patient evaluation was possible in 108 lesions. Among them, significant pain relief was seen in 98 lesions (91%). Radiological data were obtained in 83 lesions. The mass size was decreased or stable in 75 lesions and increased in eight lesions. Radiological control failure cases were hepatocellular carcinoma (5 cases), lung cancer (1 case), breast cancer (1 case) and renal cell carcinoma (1 case). Treatment-related radiation injury was not detected. Conclusion : Cyberknife radiosurgery is clinically effective and safe for spinal metastases. It is true even in previously irradiated patients. Compared to conventional radiation therapy, Cyberknife shows higher pain control rate and its treatment process is more convenient for patients. Thus, it can be regarded as a primary treatment modality for spinal metastases.