• Korean Journal of Microbiology
• /
• v.50 no.1
• /
• pp.22-26
• /
• 2014

Protocatechualdehyde (PA) is phenolic compound having antioxidative and antitumor activities. PA was purified from supernatant of Streptomyces lincolnensis M-20. In the presence of copper ion, PA acted as pro-oxidant. The antioxidant activity was assessed with the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, and the pro-oxidant effect of PA on DNA damage as pBR322 plasmid DNA-cleaving agents in the presence of Cu(II) ions was investigated. The involvement of reactive oxygen species (ROS) in the DNA damage was confirmed by the inhibition of the DNA breakage by using glutathione (GSH), specific scavenger of ROS. When the increase in ROS reaches a certain level (the toxic threshold), it may trigger cell death. The formation of the PA/Cu(II) chelate complex was confirmed by reaction with ethylenediamine-tetraacetic acid (EDTA), a well-known chelating agent for metal ions, by using UV/Vis spectroscopic analysis.

• Journal of Microbiology and Biotechnology
• /
• v.28 no.10
• /
• pp.1645-1653
• /
• 2018

The genus Acer contains several species with various bioactivities including antioxidant, antitumor and anti-inflammatory properties. However, Acer okamotoanum Nakai, one species within this genus has not been fully studied yet. Therefore, in this study, we investigated the anti-adipogenic activities of leaf extract from A. okamotoanum Nakai (LEAO) on 3T3-L1 preadipocytes. Adipogenesis is one of the cell differentiation processes, which converts preadipocytes into mature adipocytes. Nowadays, inhibition of adipogenesis is considered as an effective strategy in the field of anti-obesity research. In this study, we observed that LEAO decreased the accumulation of lipid droplets during adipogenesis and down-regulated the expression of key adipogenic transcription factors such as peroxisome proliferator-activated receptor ${\gamma}$ (PPAR ${\gamma}$) and CCAAT/enhancer binding protein ${\alpha}$ (C/EBP ${\alpha}$). In addition, LEAO inactivated PI3K/Akt signaling and its downstream factors that promote adipogenesis by inducing the expression of PPAR ${\gamma}$. LEAO also activated ${\beta}$-catenin signaling, which prevents the adipogenic program by suppressing the expression of PPAR ${\gamma}$. Therefore, we found that treatment with LEAO is effective for attenuating adipogenesis in 3T3-L1 cells. Consequently, these findings suggest that LEAO has the potential to be used as a therapeutic agent for preventing obesity.

• Development and Reproduction
• /
• v.22 no.2
• /
• pp.133-142
• /
• 2018

Patients with type II diabetes mellitus are more susceptible to colorectal cancer (CRC) incidence than non-diabetics. The anti-diabetic drug metformin is most commonly prescribed for the treatment of this disease and has recently shown antitumor effect in preclinical studies. The aberrant mutational activation in the components of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathway is very frequently observed in CRC. We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA. Therefore, we hypothesized that simultaneous inhibition of two pathways by combining metformin with BEZ235 could be more effective in the suppression of proliferation than single agent treatment in HCT15 CRC cells. Here, we investigated the combinatory effect of metformin and BEZ235 on the cell survival in HCT15 CRC cells. Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6. This combination treatment synergistically reduced cell viability. The combination index (CI) values ranged from 0.44 to 0.88, indicating synergism for the combination. These results offer a preclinical rationale for the potential therapeutic option for the treatment of CRC.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.19 no.3
• /
• pp.802-810
• /
• 2005

The tetrahydroisoquinolines included potent cytotoxic agents that showed antitumor activity,antimicrobial activity, and other biological properties. We studied the effect of CDST, 1-Chloromethyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-sulfonic acid amide, a newly synthesized anti-cancer agent. The cytotoxic activity of CDST in HL-60 cells was increased in a dose-dependent manner. CDST, tetrahydroisoquinolines derivative, was cytotoxic to HL-60 cells, with IC50 of $80{\mu}g/ml$. Treatment of CDST to HL-60 cells showed the fragmentation of DNA in a dose- and time dependent manner, suggesting that thesecells underwent apoptosis. Treatment of HL-60 cells with CDST was induced in a dose- and time-dependent activation of caspase-3, caspase-8 and proteolytic cleavage of poly(ADP-ribose) polymerase. In caspase activity assay, caspase-3 and -8 was activated after 12 h and 6 h posttreatment, respectively. CDST also caused the release of cytochrome c from mitochondria into the cytosol. CDST-induced cytochrome c release was mediated by caspase-8-dependent cleavage of Bid and Bax translocation. These results suggest that caspase-8 induced Bid cleavage and Bax translocation, caused mitochondrial cytochrome c release, and induce caspase-3 activationduring CDST-induced apoptosis in HL-60 cells.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1993.04a
• /
• pp.71-71
• /
• 1993

Carboxylesterase is widely distributed in the tissues of vertebrates, insects, plants and mycobacteria. Among various tissues of animals and humans, the highest esterase activity with various substrates is found in the liver. Kidney has moderate carboxylesterase activity in the proximal tubules. Considerable esterase activity is also found in the small intestine epithet elial cells and serum of mammals. Besides these tissues, carboxylesterase has been found in the lung, testis, adipose tissue, nasal mucosa and even in the central nervous system. Hepatic microsomal carboxylesterase catalyzes the hydrolysis of a wide variety of endogenous and exogenous compounds such as carboxylester, thioester and aromatic amide. Since carboxylesterases are important for metabolic activation of prodrugs and detoxification of xenobiotics, differences in substrate specificity and immunological properties of this enzyme are important in connection with choosing a suitable laboratory animal for the evaluation of biotransformation and toxicity of drugs. On the other hand, liver, kidney, intestine and serum were found to contain multiple forms of carboxylesterases in animal species and humans. In fact, we have purified more than fifteen isoforms of carboxylesterases from microsomes of liver, kidney and intestinal mucosa of nine animal species and humans. and characteristics of these isoforms were compared each other in terms of their physical and immunochemical properties. On the other hand, we have reported that hepatic microsomal carboxylesterases are induced by many exogenous compounds such as phenobarbital, polycyclic aromatic hydrocarbons, Aroclor 1254, aminopyrine and clofibrate. Later, we showed that some isoforms of hepatic carboxylesterase were induced by glucocorticoids such as dexamethasone and 16 ${\alpha}$-carbonitrile, but other isoforms were rather inhibited by these compounds. These findings indicate that involvement of carboxylesterases in the metabolism and toxicity of drugs should be explained by the isoforms involved. Since 1991, we have carried out detailed research investigating the types of carboxylesterases involved in the metabolic activation of CPT-11, a derivative of camptothecin, to the active metabolite, SN-38. The results obtained strongly suggest that some isoforms of carboxylesterase of liver microsomes and intestinal mucosal membrane are exclusively involved in CPT-11 metabolism. In this symposium, the properties of carboxylesterase isoforms purified from liver, kidney and intestine of animal species and humans are outlined. In addition, metabolism of CPT-11, a novel antitumor agent, by carboxylesterases in relation to the effectiveness will also be discussed.

• Biomolecules & Therapeutics
• /
• v.5 no.4
• /
• pp.369-375
• /
• 1997

General pharmacological effects of SB-31$^{R}$, the extracts of Pulsatilla koreana, were investigated in mice, rats and guinea-pigs. Intravenous injection of SB-31 (3 and 6 ml/kg) produced almost no effect on central nervous system no effects on the general symptom and behaviors of mice, spontaneous locomotor activity, pentobarbital- induced sleeping time , rotared performance , electroshock and pentylenetertrazole -induced seizures, acetic acid-induced writhing and normal body temperature in mice. SB-31 showed little effects on the spontaneous movement of the isolated ileum and contraction induced by agonists in isolated ileum, suggesting no influence on autonomic nervous system. Administration of SB-31 also did not show any effect on blood pressure in conscious rats. However, a slight decrease in heart rate was observed at high doses (6 and 10 ml/kg) of SB-31 in conscious rats. Similarly, a slight increase in respiratory rate was observed at 6 m1/kg of SB-31 in anesthetized rats. SB-31 did not produce any effect at the dose of 3 ml/kg, but showed a tendency to increase the urinary volume at 6 ml/kg, and produced a decrease in urinary excretions of N $a_{+}$and $K_{+}$at 6 ml/kg. However, transport capacity within the gastrointestinal tract and the secretion of the gastric juice were not influenced by 6 ml/kg of SB-31. In conclusion, these results suggest that SB-31 did not pro-duce any acute effects on the central nervous system, autonomic nervous system, respiratory and circulatory systems, digestive system and kidney function at the dose of below 3 ml/kg.ml/kg.

• Journal of Food Hygiene and Safety
• /
• v.13 no.2
• /
• pp.94-98
• /
• 1998

Agaricus blazei Murill, a mushroom which is well known as a potent antitumor agent, contains abundant pharmaceutical substances. To identifY the major components of Agaricus blazei Murill fruiting bodies cultivated in a Korean local farm was analyzed. There were not large differences in chemical compositions of inorganic substances, carbohydrates, amino acids and fatty acids between Agaricus blazei Murill fruiting bodies cultivated in Korea and those in Japan. However, carbohydrate composition was significantly lower in Agaricus blazei Murill of Korea compared to those of Japan. Total amino acid contents were 280.75 mg% in Agaricus blazei Murill fruiting bodies. Sixteen species of amino acid were identified by high performance liquid chromatography except cysteine. Linoleic acid, the most abundant fatty acid contained in Agaricus blazei Murill fruiting bodies, was estimated to be 78.3% of total fatty acids.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 1999.10a
• /
• pp.1-45
• /
• 1999

To date many kinds of compounds have been obtained from plants kingdom as antineoplastic and anti-cancerous agents. However, there is no special type of compounds for ncancer therapy. Various types of substances are effective for various types of cancers and tumors: for instance, alkaloids, lignans, terpenes and steroids etc. Curcumol obtained from Curcuma aromatica was tested and noticed to be effective against cancer of the uterine cervix clinically Oridonin isolated from Rabdosia ssp.is now investigated for clinical trials in China. Moreover, camptothecine isolated from Camptotheca acuminata is also antineoplastic alkaloid, but is very toxic. Chemical modification has been tried to decrease its toxicity. This compound is now using as clinical agent. Harringtonin was investigated as an anticancerous drug in China. Taxol, a compound with a taxane ring isolated from the bark of Taxus brevifolia, has been demonstrated to have substantial anticancer activity in patients with solid tumors refractory standard chemotherapy. Supply of this drug has severely limited full exploration of its antineoplastic potential. Some efforts are continued in National Cancer Institute NCI) Washington for surveying various Taxus species for optimal taxol content, improvement in semi-synthesis from baccatin III, improvement in method of extraction, and development of alternative renewable resources. Further, there are many compounds which have been reported as antineoplastic agents. On the other hand, we have screened on higher plants collected in Japan, China, Korea, Southeast Asia and South America for antineoplastic activity, which has been done using Sarcoma 180 ascites in mice, P388 Iymphocytic leukemia in mice, Chinese hamster lung V-79 cells, P388 cells and nasopharynx carcinoma (KB) cells in our laboratory, as primary screening. In this meeting, I will present on antitumor and cytotoxic substances of the higher plants (Rubia cordifolia, Ailanfhus Vilmoriniana, Aster tataricus, Taxus cuspidata var. nana, Cephalotaxus harringtonia var drupacea, etc.) selected from above screening tests.

• Korean Journal of Medicinal Crop Science
• /
• v.19 no.4
• /
• pp.287-299
• /
• 2011

Pharmacological effects of Panax ginseng have been demonstrated in cardiovascular system, endocrine secretion and immune system, together with antitumor, anti-stress and anti-oxidant activities. Modern scientific data show protective effect of ginseng against bone marrow cell death, increased survival rate of experimental animals, recovery of hematopoietic injury, immunopotentiation, reduction of damaged intestinal epithelial cells, inhibition of mutagenesis and effective protection against testicular damages, caused by radiation exposure. And also, ginseng acts in indirect fashion to protect radical processes by inhibition of initiation of free radical processes and thus reduces the radiation damages. The research has made much progress, but still insufficient to fully uncover the action mechanism of ginseng components on the molecule level. This review provides the usefulness of natural product, showing no toxic effects, as an radioprotective agent. Furthermore, the further clinical trials on radioprotection of ginseng need to be highly done to clarify its scientific application. The effective components of ginseng has been known as ginsenosides. Considering that each of these ginsenosides has pharmacological effect, it seems likely that non-saponin components might have radioprotective effects superior to those of ginsenosides, suggesting its active ingredients to be non-saponin series. These results also show that the combined effects of saponin and non-saponin components play an important role in the radioprotective effects of ginseng.

• Journal of Microbiology
• /
• v.45 no.3
• /
• pp.187-192
• /
• 2007

REOviruses (Respiratory Enteric Orphan viruses) are ubiquitous, non-enveloped viruses containing 10 segments of double-stranded RNA (dsRNA) as their genome. They are common isolates of the respiratory and gastrointestinal tract of humans but are not associated with severe disease and are therefore considered relatively benign. An intriguing characteristic of reovirus is its innate oncolytic potential, which is linked to the transformed state of the cell. When immortalized cells are transfected in vitro with activated oncogenes such as Ras, Sos, v-erbB, or c-myc, they became susceptible to reovirus infection and subsequent cellular lysis, indicating that oncogene signaling pathways are exploited by reovirus. This observation has led to the use of the virus in clinical trials as an anti-cancer agent against oncogenic tumors. In addition to the exploitation of oncogene signaling, reovirus may further utilize host immune responses to enhance its antitumor activity in vivo due to its innate interferon induction ability. Reovirus is, however, not entirely benign to immunocompromised animal models. Reovirus causes so-called "black feet syndrome" in immunodeficient mice and can also harm neonatal animals. Because cancer patients often undergo immunosuppression due to heavy chemo/radiation-treatments or advanced tumor progression, this pathogenic response may be a hurdle in virus-based anticancer therapies. However, a genetically attenuated reovirus variant derived from persistent reovirus infection of cells in vitro is able to exert potent anti-tumor activity with significantly reduced viral pathogenesis in immunocompromised animals. Importantly, in this instance the attenuated, reovirus maintains its oncolytic potential while significantly reducing viral pathogenesis in vivo.