• Journal of Society of Preventive Korean Medicine
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• v.16 no.1
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• pp.71-80
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• 2012

Objective : The aim of this study is to evaluate anti-cancer effects of $Ampelopsisradix$ Extract (AE) on human lung cancer A549 cells. Method : The apoptotic activities and cell growth arrest activities of AE were measured using 3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The molecules involved in apoptotic process were assessed by western blotting. Result : Treatment of AE potently reduced cell viability in a dose-dependent manner in A549 cells. AE (100-500 ${\mu}g/m{\ell}$) resulted in apoptosis via activation of caspase 9 following PARP cleavage in a time-and dose-dependent manner. The levels of Bax and Bad levels were increased by AE with a concomitant decrease of Bcl-xL. In addition, AE at the low dose (30 ${\mu}g/m{\ell}$) significantly inhibited cell growth in the presence of serum. Conclusion : AE has the potential as a therapeutic agent against lung cancer.

• Food Science and Biotechnology
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• v.18 no.2
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• pp.436-441
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• 2009

The final bio-metabolites of lipid peroxidation (LPO) such as 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) have been suggested to mediate the oxidative stress-linked pathological incidences. Natural phytochemicals such as polyphenolic compounds in green tea have been known in preventing the LPO induced cellular growth inhibition and apoptosis. We investigated that green tea ethanol extracts (GTE) inhibit LPO-induced apoptosis in ECV 304 cells. GTE had time- or dose-dependent anti-apoptotic effects as evidenced by changes in cell morphology, MTT assay, DNA fragmentation, LPO production, and the Western blotting for apoptotic expression. In the 4-HNE-induced apoptosis model, GTE $10-20{\mu}g/mL$ decreased cell death through decreasing LPO production. GTE protected 4-HNE induced apoptosis, as evidence with down regulation of mitochondrial signaling such as cytochrome C and caspase-3 activity. GTE increased bcl2, survival signaling protein, compared to 4-HNE alone within 6 hr incubation. Since polyphenols in GTE are effective antioxidants in endothelial ECV 304 cells, we suggested that natural polyphenols might be anti-atherosclerotic.

• Journal of Microbiology and Biotechnology
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• v.34 no.2
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• pp.240-248
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• 2024

In cancer treatment, multi-target approach has paid attention to a reasonable strategy for the potential agents. We investigated whether (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) could exert an anticancer effect by dual-regulating VEGFR2 and PPARγ. MMPP showed modulating effects in TNBC type (MDA-MB-231 and MDA-MB-468) and luminal A type (MCF7) breast cancer cell lines. MMPP enhanced PPARγ transcriptional activity and inhibited VEGFR2 phosphorylation. MMPP-induced signaling by VEGFR2 and PPARγ ultimately triggered the downregulation of AKT activity. MMPP exhibited anticancer effects, as evidenced by growth inhibition, inducement of apoptosis, and suppression of migration and invasion. At the molecular level, MMPP activated pro-apoptotic proteins (caspase3, caspase8, caspase9, and bax), while inhibiting the anti-apoptotic proteins (bcl2). Additionally, MMPP inhibited the mRNA expressions of EMT-promoting transcription factors. Therefore, our findings showed molecular mechanisms of MMPP by regulating VEGFR2 and PPARγ, and suggested that MMPP has potential to treat breast cancer.

• Natural Product Sciences
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• v.18 no.1
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• pp.26-31
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• 2012

Actinidia arguta (Actinidiaceae) has been reported to have several pharmacological effects such as anti-inflammatory, anti-allergic, and anti-oxidant activities. The present study investigated the protective activity of an ethanol extract from the leaf and stem of A. arguta against glutamate-induced neurotoxicity using cultured rat cortical neurons. Exposure of cultured cortical neurons to $500{\mu}M$ glutamate for 12 h triggered neuronal cell death. A. arguta inhibited glutamate-induced neuronal death and apoptosis, which were measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining, respectively. The increase of pro-apoptotic proteins, Bax and c-caspase-3, in glutamate-treated neurons was significantly inhibited by treatment with A. arguta. A. arguta also inhibited $500{\mu}M$ glutamate-induced elevation of intracellular calcium concentration ($[Ca^{2+}]_i$) and reactive oxygen species (ROS) generation, which were measured by fluorescent dyes, Fluo-4 AM and $H_2DCF$-DA, respectively. These results suggest that A. arguta may prevent glutamate-induced apoptotic neuronal death by inhibiting $[Ca^{2+}]_i$ elevation and ROS generation and, therefore, may have a therapeutic role for the prevention of neurodegeneration in cerebral ischemic diseases.

• Journal of Pharmacopuncture
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• v.20 no.3
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• pp.158-172
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• 2017

Nigella sativa (N. sativa, family Ranunculaceae) is a medicinal plant that has been widely used for centuries throughout the world as a natural remedy. A wide range of chemical compounds found in N. sativa expresses its vast therapeutic effects. Thymoquinone (TQ) is the main component (up to 50%) in the essential oil of N. sativa. Also, pinene (up to 15%), p-cymene (40%), thymohydroquinone (THQ), thymol (THY), and dithymoquinone (DTQ) are other pharmacologically active compounds of its oil. Other terpenoid compounds, such as carvacrol, carvone, 4-terpineol, limonenes, and citronellol, are also found in small quantities in its oil. The main pharmacological characteristics of this plant are immune system stimulatory, anti-inflammatory, hypotensive, hepatoprotective, antioxidant, anti-cancer, hypoglycemic, anti-tussive, milk production, uricosuric, choleretic, anti-fertility, and spasmolytic properties. In this regard, we have searched the scientific databases PubMed, Web of Science, and Google Scholar with keywords of N. sativa, anti-cancer, apoptotic effect, antitumor, antioxidant, and malignancy over the period from 2000 to 2017. The effectiveness of N. sativa against cancer in the blood system, kidneys, lungs, prostate, liver, and breast and on many malignant cell lines has been shown in many studies, but the molecular mechanisms behind that anti-cancer role are still not clearly understood. From among the many effects of N. sativa, including its anti-proliferative effect, cell cycle arrest, apoptosis induction, ROS generation, anti-metastasis/anti-angiogenesis effects, Akt pathway control, modulation of multiple molecular targets, including p53, p73, STAT-3, PTEN, and $PPAR-{\gamma}$, and activation of caspases, the main suggestive anti-cancer mechanisms of N. sativa are its free radical scavenger activity and the preservation of various anti-oxidant enzyme activities, such as glutathione peroxidase, catalase, and glutathione-S-transferase. In this review, we highlight the molecular mechanisms of apoptosis and the anti-cancer effects of N. sativa, with a focus on its molecular targets in apoptosis pathways.

• The Korea Journal of Herbology
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• v.28 no.6
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• pp.79-86
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• 2013

Objectives : The purpose of this study is to investigate neuroprotective effects and molecular mechanisms of luteolin against ${\beta}$-amyloid ($A{\beta}_{25-35}$)-induced oxidative cell death in BV-2 cells. Methods : The protective effects of luteolin against $A{\beta}_{25-35}$-induced cytotoxicity and apoptotic cell death were determined by MTT dye reduction assay and TUNEL staining, respectively. The apoptotic cell death was further analyzed by measuring mitochondrial transmembrane potential and expression of pro- and/or anti-apoptotic proteins. To elucidate the molecular mechanisms underlying the protective effects of luteolin, intracellular accumulation of reactive oxygen species, oxidative damages, and expression of antioxidant enzymes were examined. Results : Luteolin pretreatment effectively attenuated $A{\beta}_{25-35}$-induced apoptotic cell death indices such as DNA fragmentation, dissipation of mitochondrial transmembrane potential, increased Bax/Bcl-2 ratio, and activation of c-Jun N-terminal kinase and caspase-3 in BV-2 cells. Furthermore, $A{\beta}_{25-35}$-induced intracellular formation of reactive oxygen species and subsequent oxidative damages such as lipid peroxidation and depletion of endogenous antioxidant glutathione were suppressed by luteolin treatment. The neuroprotective effects of luteolin might be mediated by up-regulation of cellular antioxidant defense system via up-regulation of ${\gamma}$-glutamylcysteine ligase, a rate-limiting enzyme in the glutathione biosynthesis and superoxide dismutase, an enzyme involved in dismutation of superoxide anion into oxygen and hydrogen peroxide. Conclusions : These findings suggest that luteolin has a potential to protect against $A{\beta}_{25-35}$-induced neuronal cell death and damages thereby exhibiting therapeutic utilization for the prevention and/or treatment of Alzheimer's disease.

• Journal of Life Science
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• v.19 no.8
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• pp.1073-1080
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• 2009

A number of studies have demonstrated that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risks of colorectal, oesophageal and lung cancers. NSAIDs have been shown to exert their anti-cancer effects through inducing apoptosis in cancer cells. The susceptibility of tumor cells to anti-tumor drug-induced apoptosis appears to depend on the balance between pro-apoptotic and anti-apoptotic programs such as nuclear factor kB (NF-kB), phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) and MEK1/2-ERK1/2 pathways. We examined the effects of pro-survival PI3K and ERK1/2 signal pathways on cell cycle arrest and apoptosis in response to NSAIDs including sulindac sulfide and NS398. We show that simultaneous inhibition of the Akt/PKB and ERK1/2 signal cascades could synergistically enhance the potential pro-apoptotic activities of sulindac sulfide and NS398. Similar enhancement was observed in cells treated with sulindac sulfide or NS398 and 100 ${\mu}$M genistein, an inhibitor of receptor tyrosine kinases (RTKs) that are upstream of PI3K and MEK1/2 signaling. We further demonstrate that NAG-1 is induced and plays a critical role(s) in apoptosis by NSAIDs-based combined treatment. In sum, our results show that combinatorialtreatment of sulindac sulfide or NS398 and genistein results in a highlysynergistic induction of apoptotic cell death to increase the chemopreventive effects of the NSAIDs, sulindac sulfide and NS398.

• CELLMED
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• v.3 no.1
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• pp.1.1-1.7
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• 2013

The present review investigates the role of the cytoprotective enzyme heme oxygenase-1 (HO-1) in human diseases and explores strategies for its clinical use. In recent years, there has been a growing evidence, for the beneficial effects of some phytoconstituents via induction of HO-1 expression, contained in commonly used spices, fruits, and herbs, in preventing various pathologic conditions, including cancer, diabetes, and cardiovascular diseases. HO-1 catalyzes the rate-limiting step in heme catabolism to generate ferrous iron, carbon monoxide, and biliverdin. HO-1 is reported to play crucial roles in cellular protection, such as anti-inflammatory, anti-proliferative and anti-apoptotic effects. These evidences indicate that HO-1 may functions as a potential therapeutic target in various human diseases. The article highlights the current status of the development of the HO-1 modulation pathway using dietary phytoconstituents.

• Journal of Ginseng Research
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• v.36 no.4
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• pp.342-353
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• 2012

Ginseng, the root of the Panax ginseng, has been a popular and widely-used traditional herbal medicine in Korea, China, and Japan for thousands of years. Now it has become popular as a functional health food and is used globally as a natural medicine. Evidence is accumulating in the literature on the physiological and pharmacological effects of P. ginseng on neurodegenerative diseases. Possible ginseng- or ginsenosides-mediated neuroprotective mechanisms mainly involve maintaining homeostasis, and anti-inflammatory, anti-oxidant, anti-apoptotic, and immune-stimulatory activities. This review considers publications dealing with the various actions of P. ginseng that are indicative of possible neurotherapeutic efficacies in neurodegenerative diseases and neurological disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis and multiple sclerosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1108-1117
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• 2007

To investigate the possible mechanism of ${\alpha}-spinasterol$ as a candidate of anti-cancer drug, I examined the effects of ${\alpha}-spinasterol$ on the apoptosis of U937 cells MTT assay, flow cytometric analysis, SDS-polyacrylamide gel electrophoresis, Western blot analysis, and RT-PCR were performed. ${\alpha}-spinasterol$ treatment reduced the cell viablilty of U937 cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death. ${\alpha}-spinasterol$ treatment also reduced the levels of Bcl-xL anti-apoptotic protein expression and increased the levels of caspase-3, p53, pro-apoptotic protein, in U937 cells. After treatment the level of Bcl-xL, anti-apoptotic gene expression was decreased and the level of ICE pro-apoptotic gene expression was increased. These findings suggest that ${\alpha}-spinasterol$ induced the apoptotic cell death via regulation of several growth regulatory gene products. The abbreviations used are: FBS, fetal bovine serum; PBS, phosphate buffered saline; PI, propidium iodide; OD, optical density; DiOC6, 3,3-dihexyloxa carbcyanine iodide; MTT, 3 [4-5-dimethylthiazol-2-yl] -2-diphenyltetrazolium bromide.