• Korean Journal of Pharmacognosy
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• v.40 no.1
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• pp.46-50
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• 2009

The antitumor activity of the roots extract of Pueraria thunbergiana was investigated on the basis of cytotoxicity upon the cultured human tumor cell lines, in vitro. The purification of methylene chloride (MC) soluble part and ethylacetate (EA) soluble part of extract by column chromatography furnished seven isoflavonoids, two triterpenoids, one but-2-enolide. The structures of them were established by chemical and spectroscopic means to be lupeol (1), $\beta$-sitosterol (2), biochanin A (3), (-)-tuberosin (4), calycosin (5), daidzein (6), puerarin (7), daidzin (8), (+)-puerol-B 2-O-$\beta$-glucopyranoside (9), formononetin-7-O-$\beta$-glucopyranoside (10). Each isolates ($1{\sim}10$) were evaluated for inhibitory activities on the proliferation of cultured human tumor cell lines such as A549, SK-OV-3, HCT-15 and SK-MEL-2, respectively.

• Molecules and Cells
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• v.22 no.1
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• pp.70-77
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• 2006

Platelets are anucleate cytoplasmic fragments derived from bone marrow megakaryocytes, and endothelial cells constitute the barrier between bloodstream and adjacent tissues. Although platelets are thought to regulate the biological functions of endothelial cells, the molecular mechanisms involved are poorly understood. With human umbilical vein endothelial cells and freshly isolated platelets, we established an in vitro model of platelet-induced endothelial cell proliferation. Platelets stimulated endothelial cell proliferation in a dose-dependent manner and transwell experiments with semi-permeable membranes suggested that direct cell-to-cell contacts were required. We developed mAbs against platelets and selected a mAb that blocks their proliferative effect. We purified the antigen by immunoprecipitation and identified it by Q-TOF MS analysis as the tetraspanin CD9. Since both platelets and endothelial cells expressed CD9 strongly on their surfaces we carried out a pre-treatment experiment that showed that CD9 molecules on the endothelial cells participate in the mitogenic effect of the platelets. The inhibitory effect of our mAb was comparable to that of a well-known functional anti-CD9 mAb. These results suggest that the tetraspanin CD9 plays an important role in endothelial regeneration.

• Animal cells and systems
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• v.1 no.1
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• pp.151-155
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• 1997

Promoter of the Drosophila proliferating cell nuclear antigen (PCNA) gene contains DRE (Drosophila DNA replication-related element) required for the high level expression of replication-related genes. Recently, we found that promoter region of the D-raf (a Drosophila homolog of the human c-raf-1) contains two sequences homologous to the DRE and demonstrated the DRE/DREF (DRE-binding factor) involvement in regulation of the D-raf gene. In this study, using ursolic acid (UA), a pentacyclic triterpene acid reported to possess antitumor activities, we examined effects of UA on proliferation of the Drosophila cultured Kc cells and on expression of the PCNA and D-raf genes. UA showed an inhibitory effect on proliferation of the Kc cells in a concentration-dependent manner in DNA content assays and [3H]thymidine incorporation assays. The IC50 value of anti-proliferative effects of UA in DNA content assays was about 7.5uM. UA showed inhibitory effects on expression of the PCNA as well as on that of the D-raf, which were examined with the reporter plasmic p5'-168DPCNACAT or p5'-878DrafCAT, respectively. The results obtained in the present study suggest that expression of the PCNA and D-raf genes is coordinately regulated in at least UA-treated Kc cells and that down-regulation of expression of the PCNA and D-raf genes might be related with the antitumor activities of UA.

• YAKHAK HOEJI
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• v.60 no.3
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• pp.101-106
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• 2016

Allylthiopyridazine derivatives were synthesized and evaluated for anti-proliferative activities in the previous study. In this study, selected two allylthiopyridazine derivatives (compound I, 3-heptylamino-6-allylthiopyridazine and compound II, 3-dipentylamino-6-allylthiopyridazine) were assessed for cytotoxicity and chronic proliferation in human colon carcinoma RKO cells. Two derivatives dose-dependently inhibited cell viability and proliferation. To elucidate the anticancer mechanism of two derivatives, we investigated the expression level of apoptosis-related proteins in RKO cells. Compound I induced the activation of JNK and expression of p53 and p21. On the other hand, compound II showed no change of p53 level. Interestingly, compound II inhibited the nuclear translocation of NF-${\kappa}B$. This result suggested that compound II suppressed cell proliferation. These different mechanisms of these compounds might have occurred through different steric conformation.

• Korean Journal of Plant Resources
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• v.29 no.3
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• pp.297-304
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• 2016

The seed of safflower (Carthamus tinctorius L) has been reported to suppress human cancer cell proliferation. However, the mechanisms by which safflower seed inhibits cancer cell proliferation have remained nuclear. In this study, the inhibitory effect of the safflower seed (SS) on the proliferation of human colorectal cancer cells and the potential mechanism of action were examined. SS inhibited markedly the proliferation of human colorectal cancer cells (HCT116, SW480, LoVo and HT-29). In addition, SS suppressed the proliferation of human breast cancer cells (MDA-MB-231 and MCF-7). SS treatment decreased cyclin D1 protein level in human colorectal cancer cells and breast cancer cells. But, SS-mediated downregulated mRNA level of cyclin D1 was not observed. Inhibition of proteasomal degradation by MG132 attenuated cyclin D1 downregulation by SS and the half-life of cyclin D1 was decreased in SS-treated cells. In addition, SS increased cyclin D1 phosphorylation at threonine-286 and a point mutation of threonine-286 to alanine attenuated SS-mediated cyclin D1 degradation. Inhibition of ERK1/2 by PD98059 suppressed cyclin D1 phosphorylation and downregulation of cyclin D1 by SS. In conclusion, SS has anti-proliferative activity by inducing cyclin D1 proteasomal degradation through ERK1/2-dependent threonine-286 phosphorylation of cyclin D1. These findings suggest that possibly its extract could be used for treating colorectal cancer.

• Journal of Life Science
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• v.10 no.1
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• pp.22-36
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• 2000

The mammary gland contains a subpopulation of epithelial cells with large proliferative potentials which are the likely targets for carcinogens. These clonogenic cells can proliferate and differentiate into functional glandular structures. Multicellular secretory alveolar units (AU) develop from these clonogens in grafts of monodispersed rat mammary epithelial cells (RMEC) in gland-free mammary fat pads in intact recipient F344 rats co-grafted with mammotropic hormone-secreting pituitary tumors (MtT F4). Multicellular nonsecretory ductal units (DU) develop in grafts of monodispersed RMEC in gland-free fat pads in adrenalectomized recipient WF rats co-grafted with MtT W10. However, this effect were reversed by hydrocortisone replacement therapy. RMEC were isolated from appropriate donor rats as monodispersed mixed cells or, alternatively, RNA＋ cells were sorted by flow cytometry of mixed RMEC stained with FITC-RNA and PE-anti-Thy-1.1 monoclonal antibody. We grafted mixed or sorted PNA+ cells in gland-free mammary fat pads in recipient rats that were endocrinologically manipulated to induce AU or DU. Cells were also isolated from these AU or DU as mixed or sorted RNA＋ cells and sub-transplanted in recipient rats treated appropriately to induce AU or DU, respectively. Cells obtained from AU in grafts gave rise to clonal AU and from DU in grafts to DU on sub-transplantation in appropriate recipients. When adrenalectomized recipient WF rats co-grafted with MtT W10 received daily subcutaneous injections of hydrocortisone for periods of 21 days following the PHA＋ cell transplantation, AU, instead of DU, were developed. The histologies of these secondary AU and DU were not different from those of the primary AU and DU. Casein and laminin proteins were demonstrated by immunocytochemical staining of primary and secondary AU. Electron micrographs also demonstrated that AU were composed of secretory cells with milk protein in the cytoplasm. DU were composed of little or non-secretory ductal epithelial cells. These AU and DU also secreted large amounts of lipids. Clonogenic cells were more common in DU than in AU. Thus, AU and DU contain persistent subpopulations of clonogenic stem-like cells.

• Journal of Nutrition and Health
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• v.38 no.7
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• pp.503-511
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• 2005

In this study we investigated the biological activity of Chondria Crassicaulis (CC) on the human cancer cells. CC was extracted with methanol and further fractionated into four different types: hexane (CCMH), methanol (CCMM), butanol (CCMB), and aqueous (CCMA) partition layers. We determined the cytotoxic effect of these layers on human cancer cells by MTT assay. Among various partition layers of CC, the CCMM and CCMB showed the strong cytotoxic effects at 150 ${\mu}g$/ml which resulted $98.91\%$, $92.96\%$ on HeLa cell lines and $95.47\%$, $77.05\%$ on MCF-7 cell lines. And, the anti-proliferative effect of CC was accompanied by a marked inhibition of cyclooxygenase (COX-2), Caspase-3 and IAP (cIAP-1, cIAP-2 and XIAP) protein and concomitant induction of p53, p21 and Survivin protein. However, CC did not affect the level of Bax, Bcl-2 and Bcl-XL- protein. Also, we observed quinone reductase (QR) induced effects in all fraction layers of CC on HepG2 cells. The QR induced effects of the CCMH and CCMM on HePG2 cells at 120 ${\mu}g$/mL concentration indicated 3.73 and 2.45 with the control value of 1.0. Although further studies are needed, the present work suggests that CC may be a chemopreventive agent for the treatment of human cancer cells.

• Journal of Chitin and Chitosan
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• v.23 no.4
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• pp.256-261
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• 2018

Recently, the number of cardiovascular disease-related deaths worldwide has increased. Therefore, the importance of percutaneous cardiovascular intervention and drug-eluting stents (DES) has been highlighted. Despite the great clinical success of DES, the re-endothelialization at the site of stent implantation is retarded owing to the anti-proliferative effect from the coated drug, resulting in late thrombosis or very late restenosis. In order to solve this problem, studies have been actively carried out to excavate new drugs that promote rapid re-endothelialization. In this study, we introduced hydrophilic drug, tauroursodeoxycholate (TUDCA), that improves the proliferation of endothelial progenitor cells and promotes apoptosis of vascular smooth muscle cells. In addition, we utilized shellac, which is a natural resin from lac bug to coat TUDCA on the surface of the metal. When using conventional coating method including biodegradable polymers and organic solvents, phase separation between polymer and drug occurred in the coating layer that caused incomplete incorporation of drug into the polymer layer. However, when using shellac as a coating polymer, no phase separation was observed and drug was fully covered with the polymer matrix. In addition, by adjusting the composition of coating solution and modifying the hydrophilicity of the metal surface using oxygen plasma, the surface roughness decreased due to the increased affinity between coating solution and metal surface. This result provides a method of depositing a hydrophilic drug layer on the stent.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.52 no.1
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• pp.35-42
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• 2019

We investigated the protective effects of antioxidant fractions from a 70% ethanolic extract of Hizikia fusiformis in human dermal fibroblasts (HDFs). Powdered H. fusiformis was extracted with 70% ethanol and then partitioned into three fractions according to polarity using n-hexane (HFH), chloroform (HFC), and ethyl acetate (HFEA). Antioxidant activity was observed in HFEA at 0.66 mg/mL based on the half maximal inhibitory concentration ($IC_{50}$) of 1,1-diphenyl-2-picrylhydrazyl (DPPH), and at 0.24 mg/mL based on alkyl radical scavenging. The protective effects of the HFEA antioxidant fraction against 2,2-azobis-(2-amidinopropane) dihydrochloride (AAPH)-damaged HDFs and the expression of Type I procollagen in HDFs were examined. HFEA caused the proliferation of HDFs with and without AAPH treatment and protected against AAPH damage to HDFs in a dose-dependent manner ($50-200{\mu}g/mL$). This implies that the antioxidant properties of the fractions depended on their proliferative and protective effects. The HFEA antioxidant fraction had significant effects and caused the dose-dependent expression of Type I procollagen, an important anti-wrinkle protein, in HDFs. In conclusion, antioxidant substances in H. fusiformis were found in the ethyl acetate fraction, and the resulting HFEA may have cosmetic applications.

• International Journal of Oral Biology
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• v.46 no.1
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• pp.23-29
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• 2021

Demethoxycurcumin (DMC), which is a curcuminoid found in turmeric, has anti-proliferative effects on cancer cells. However, the effect of DMC on osteosarcoma has not been established. The aim of this study was to examine the effects of DMC on cell growth and apoptosis induction in MG-63 human osteosarcoma cells. This study was investigated using 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromid assay, Live/Dead cell assay, 4', 6-diamidino-2-phenylindole staining, and immunoblotting in MG-63 cells. DMC induced MG-63 cell death in a dose-dependent manner, with an estimated IC50 value of 54.4 µM. DMC treatment resulted in nuclear condensation in MG-63 cells. DMC-induced apoptosis in MG-63 cells was mediated by the expression of Fas and activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting results showed that Bcl-2 and Bcl-xL were downregulated, while Bax and Bad were upregulated by DMC in MG-63 cells. These results indicated that DMC inhibits cell proliferation and induces apoptotic cell death in MG-63 human osteosarcoma cells via the death receptor-mediated extrinsic apoptotic pathway and mitochondria-mediated intrinsic apoptotic pathway.