• Korean Journal of Fisheries and Aquatic Sciences
• /
• v.31 no.4
• /
• pp.587-593
• /
• 1998

To elucidate anti-tumor promoter from seaweed, the anti-tumor promoting activity of Ecklonia stolonifera, Undaria pinnatifida and Laminaria japonica extracts were determined by Epstein-Barr virus (EBV)-early antigen (EA) induction caused by a tumor promoter, teleocidin B-4. The methanol extracts of seaweed were subsequently fractionated with diethyl ether, distilled water, chloroform and ethyl acetate. Among the solvent fractions tested, chloroform and ethyl acetate fraction of E. stolonifera showed a high anti-tumor promoting activity at the levels of 88.0 and $85.9\%$ by the addition of 20 ${\mu}g/m{\ell}$, respectively. To characterize anti-tumor promoters from solvent fractions of E. stolonifera, the effects of phenols, chlorophyll derivatives and carotenoids on the anti-tumor promoting activity were investigated. Phenols, such as bromophenol and phloroglucinol showed anti-tumor promoting activity of $57\~66\%$ at 20 ${\mu}g/m{\ell}$. Pigments, such as chlorophylls and carotenoids exerted high anti-tumor promoting activities. Chlorophyll a and pheophorbide a exhibited the activity of $77.4\%$ and $66.6\%$ at 5${\mu}M/m{\ell}$, respectively. The active compounds of carotenoids were tentatively identified as lutein and $\alpha-cryptoxanthin$ from the profiles of visible spectra and R_f value of their authentic compounds, and showed anti-tumor promoting activities of $76.9\%$ and $84.4\%$ at dose of 20 ${\mu}g/m{\ell}$, respectively.

• Korean Journal of Fisheries and Aquatic Sciences
• /
• v.29 no.6
• /
• pp.917-919
• /
• 1996

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.27 no.3
• /
• pp.537-542
• /
• 1998

The present study was performed to elucidate desmutagenic principles from Ecklonia stolonifera extracts against 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine(PhIP) and 2-amino-3,8-dime-thylimidazo[4,5-f]duinoxaline(MeIQx) with Salmonella/mammalian-microsome mutagenicity test. Alginate, phenols, chlorophyll and carotenoids from Ecklonia stolonifera were extracted and their desmutagenicities were assayed. Alginate hydroysates showed desmutagenic activities against PhIP and MeIQx at high level dose. Phenol fractions and bromophenol showed desmutagenic activity of about MeIQx at high level dose. Phenol fractions and bromophenol showed desmutagenic activity of about 90% per 0.5mg against PhIP and MeIQx. Chlorophyllin among chlorophyll derivatives exhibited remarkable desmutagenic activities of 92.9% and 82.7% at 20uM against PhIP and MeIQx, respectively. Carotenoids, such as lutein and $\alpha$-cryptoxanthin isolated from Ecklonia stolonifera exerted also high desmutagenic activity. Major desmutagenic substances from Ecklonia stolonifera are considered to be chlorophyllin, phenols, lutein, $\alpha$-cryptoxanthin and low molecular alginates.

• Korean Journal of Fisheries and Aquatic Sciences
• /
• v.31 no.4
• /
• pp.581-586
• /
• 1998

The present study was conducted to prepare seaweed extracts suppressing mutagenic activity of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine ( PhIP ) ana 2-amino-3,8-dimethylmidazo[4,5-f]quinoxaline (MeIQx) derived from cooked meat produce. The tumor initiation activity of PhIP and MeIQx was assayed with Ames method using Salmonella typhimurium TA98 in the presence of S-9 mixtures before and after addition of methanol-solubles of seaweed, such as, Phaeophyta; Undaria pinnatifida, Ecklonia stolonifera Ecklonia cava, Laminaia japonica Sargassum fulvellum, Sargassum hornezi, Sargassum miyabei, Sargassum thunbergii, Agarum cribrosum and Hizikia fusifomis, Rhodophpei Porphyra yezoensis, Grateloupia eiliptiut Lomentraria catenata, Ploemium telfairiae and Glarilaria verrucosa, Chlorophyta; Codium fragile, Enteromorpha compresa and Ulva pertusa. Among seaweed tested, Phaeophyta was shown the higher desmutagenic activity than Rhodophyta and Chlorophyta. E. stolonifera, E. cava and S. miyabei, among Phaeophyta exerted the stronger desmutagenic activity (above $90\%$/2 mg). The ethyl acetate, diethyl ether and chlomform extracts except water extracts from E. stolonifera exhibited a high desmutagenic activity. The ethyl acetate extract of E. stolonifera which showed highest activity was fractionated with Sephadex LH20 column chromatography to give active fraction A-7, which showed desmutagenicity of $90\%$/mg against PhIP and $80\%$/mg against MeIQx. The active fraction had the absorbance at 207.7 and 232nm.

• Journal of Photoscience
• /
• v.9 no.2
• /
• pp.221-224
• /
• 2002

Carcinogenesis can be theoretically divided to intiation step and promotion step. Intiation associates with genetic alterations including p53 tumor suppressor gene and ras oncogene. Promotion involves in clonal expansion of of an initiated cell by epigenetic mechanism, mainly through signal transduction and gene expression. Ultraviolet light (UV) acts as both initiator and promoter. Initiation is closely related with DNA damage induced by UV, including cyclobutane pyrimidine dimers, (6-4) photoproducts and 8-hydroxy-2'-deoxyguanosine. Cyclobutane pyrimidine dimers and (6-4) photoproducts are directly induced by UV, while 8-hydroxy-2'-deoxyguanosine is induced indirectly by the reactive oxygen species. Because initiation is an irreversal genetic event, while promotion is a reversal and epigenetic event, to know the molecular mechanisms of tumor promotion in UV-carcinogenesis is crucial to develop preventive medicine and suppress UV-carcinogenesis. Because ROS is also involved in signal transduction of the cell, anti-oxidant could be the good candidate of anti-promoting agent. Here, we describe the suppressive effect of UV-carcinogenesis by various anti-oxidant including olive oil. In addition, we discuss about the mechanism of UVB-induced expression of cyclooxygenase-2, which might be a representative molecule involved in promotion of UV-carcinogenesis.

• Journal of Life Science
• /
• v.26 no.7
• /
• pp.847-854
• /
• 2016

Cordycepin, a derivative of the nucleoside adenosine, is one of the active components extracted from fungi of genus Cordyceps, and has been shown to have many pharmacological activities. In this study, we investigated the effects of cordycepin on proliferation and apoptosis of human gastric cancer AGS cells, and its possible mechanism of action. Treatment of cordycepin resulted in significant decrease in cell viability of AGS cells in a concentration-dependent manner. A concentration-dependent apoptotic cell death was also measured by agarose gel electrophoresis and flow cytometery analysis. Molecular mechanistic studies of apoptosis unraveled cordycepin treatment resulted in an enhanced expression of tumor necrosis factor-related apoptosis-inducing ligand, death receptor 5 and Fas ligand. Furthermore, up-regulation of pro-apoptotic Bax, and down-regulation of anti-apoptotic Bcl-2 and Bcl-xL expression were also observed in cordycepin-treated AGS cells. These were followed by activation of caspases (caspase-9, -8 and -3), subsequently leading to poly (ADP-ribose) polymerase cleavage. Taken together, these findings indicate that cordycepin induces apoptosis in AGS cells through regulation of multiple apoptotic pathways, including death receptor and mitochondria. Although further mechanical studies are needed, our results revealed that cordycepin can be regarded as a new effective and chemopreventive compound for human gastric cancer treatment.

• Journal of Life Science
• /
• v.29 no.10
• /
• pp.1062-1070
• /
• 2019

A components of garlic (Allium sativum) have anti-proliferative effects against various types of cancer. We aimed to investigate the capacity of garlic compounds to anti-tumor on a various cancer cell lines. Fractionation of garlic extract, guided by antiproliferative activity against human gastric cancer (AGS) cells, has resulted in the isolation of N-benzyl-N-methyldecan-1-amine (NBNMA). We investigated the effect of newly isolated NBNMA from garlic cloves on the inhibition of the growth of CT-26, AGS, HepG2, HCT-116, MCF7, B16F10, and Sarcoma-180 cells for in vitro and CT-26 colon carcinoma cells in vivo. NBNMA exhibited an antiproliferative effect in CT-26 cells by apoptotic cell death. NBNMA exhibited down-regulation of anti-apoptotic Bcl-2 proteins and up-regulation of apoptotic Bad protein expression in western blot analyses. In addition, NBNMA meagre activated caspase 3 and caspase 9, initiator caspases of the extrinsic and intrinsic pathways of apoptosis. NBNMA treatment at a dose of 10 mg/kg for 21 days in experimental mice implanted with tumors resulted in significant reduction of the tumor weight (43%). NBNMA exhibited both in vitro and in vivo anticancer activity. These results indicate that NBNMA has promising potential to become a novel anticancer agent from garlic cloves for the treatment of colon carcinoma cancer.

• Journal of Life Science
• /
• v.25 no.11
• /
• pp.1235-1243
• /
• 2015

Hwangheuk-san (HHS) is a Korean multi-herb formula comprising four medicinal herbs. HHS, which was recorded in “Dongeuibogam,” has been used to treat patients with inflammation syndromes and digestive tract cancer for hundreds of years. However, little is known about its anti-tumor efficacy. The present study investigated the pro-apoptotic effect and mode of action of HHS against AGS human gastric carcinoma cells. HHS inhibited the cell growth of AGS cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, chromatin condensation, and an accumulation of cells in the sub-G1 phase. HHS-induced apoptotic cell death was associated with the up-regulation of pro-apoptotic Bax protein expression, down-regulation of antiapoptotic Bcl-2 protein, and the release of cytochrome c from mitochondria to the cytosol. The treatment of AGS cells with HHS significantly elevated the generation of reactive oxygen species (ROS). Additionally, apoptosis-inducing concentrations of HHS induced the activation of both caspase-9 and -8, initiator caspases of the mitochondrial-mediated intrinsic and death receptor-mediated extrinsic pathways, respectively, and caspase-3, accompanied by proteolytic degradation of poly (ADP-ribose)-polymerase. However, ROS scavenger and pan-caspases inhibitor significantly blocked HHS-induced growth inhibition and apoptosis. Taken together, these findings suggest that HHS induces apoptosis through ROS- and caspase-dependent mechanisms and that HHS may be a potential chemotherapeutic agent for the control of human gastric cancer.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.44 no.7
• /
• pp.975-982
• /
• 2015

Piceatannol (trans-3,4,3',5'-trihydroxystilbene), a natural stilbene, is an analogue of resveratrol. In the present study, possible mechanisms by which piceatannol exerts its pro-apoptotic action in cultured human oral cancer YD-15 cells were investigated. To investigate whether or not piceatannol has effects on cancer cell viability, human oral YD-15 cells were treated with piceatannol (0, 50, and $100{\mu}M$). Piceatannol treatment ($100{\mu}M$) showed the strongest inhibition of cell proliferation and reduced cell viability in a dose-dependent manner. Chromatin condensation detected by DAPI staining significantly increased in a concentration-dependent manner, indicating apoptosis. Piceatannol treatment activated initiator Bax (pro-apoptotic) and cPARP in a concentration-dependent manner. Further, piceatannol induced down-regulation of Bcl-2 (anti-apoptotic). We also evaluated the activity of piceatannol against oral cavity cancer tumors in mice. Piceatannol-treated nude mice bearing YD-15 xenograft tumors exhibited significantly reduced tumor volume and weight due to the potent effect of piceatannol on tumor cell apoptosis, as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Immunohistochemistry staining showed elevated expression of cleaved-caspase-3 as well as reduced expression of Ki-67 in the piceatannol-treated group. Therefore, piceatannol can be developed as a cancer preventive medicine due to its growth inhibitory effects and induction of apoptosis in human oral cancer cells.