PubMed Health⌕ Search

Biomedical subjects

Dong-Kyoo Kim

Publications and source records attributed to Dong-Kyoo Kim.

6 recordsLinked to original sources
PubMed2005

Mechanism of cell cycle arrest by (8E,13Z,20Z)-strobilinin/(7E,13Z,20Z)-felixinin from a marine sponge Psammocinia sp.

Furanosesterterpenes, isolated from a marine sponge Psammocinia sp. have been reported to display significant cytotoxicity to some cancer cell lines. In this study, EZZ, an inseparable 1:1 mixture of (8E,3Z,20Z)-strobilinin and (7E,3Z,20Z)-felixinin, showed significant antiproliferative effect on human cervix carcinoma cell line (HeLa). Cell cycle analysis revealed that EZZ could arrest HeLa cells in S phase with a concomitant decrease in the cell population of G1 phase. By using simian virus (SV40) DNA in vitro replication system, we found that EZZ could inhibit DNA replication, which suggests that EZZ-induced S phase arrest might be the direct result of blocked DNA synthesis. Furthermore, low concentration of EZZ was found to be capable of significantly inhibiting the DNA cleavage by topoisomerase I (topo I) and reducing the polymerase alpha-primase (pol alpha-primase) activity, while the ssDNA binding activity of replication protein A (RPA) was less affected. Taken together, these results suggest that EZZ-induced cell cycle arrest in S phase correlate with the inhibition of DNA replication, and topo I and pol alpha-primase might be the two main target molecules.

Animals↗
PubMed2004

Cytotoxicity of psammaplin A from a two-sponge association may correlate with the inhibition of DNA replication.

BACKGROUND: SV40 DNA replication system is a very useful tool to understand the mechanism of replication, which is a tightly regulated process. Many environmental and cellular factors can induce cell cycle arrest or apoptosis by inhibiting DNA replication. In the course of our search for bioactive metabolites from the marine sponges, psammaplin A was found to have some anticancer properties, the possible mechanism of which was studied. METHODS: Cell viability was determined by Cell Counting Kit-8 (CCK-8) to count living RAW264.7 cells by combining 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-8) and 1-methoxy-phenazine methosulfate (1-methoxy-PMS). The effect of psammaplin A on DNA replication was carried out in SV40 DNA replication system in vitro. The activities of topoisomerase I and polymerase alpha-primase were measured by the relaxation of superhelical plasmid DNA and the incorporation of [3H]dTTP to the template respectively. The ssDNA binding activity of RPA was assessed by Gel Mobility Shift Assay (GMSA). RESULTS: We have found that psammaplin A delivers significant cytotoxic activity against the RAW264.7 cell line. It was also found that psammaplin A could substantially inhibit SV40 DNA replication in vitro, in which polymerase alpha-primase is one of its main targets. CONCLUSION: Taken together, we suggest that psammaplin A-induced cytotoxicity may correlate with its inhibition on DNA replication. Psammaplin A has the potential to be developed as an anticancer drug.

Animals↗
PubMed2004

Cytotoxic furanosesterterpenes from a marine sponge Psammocinia sp.

Three new (1-3) and seven known (4-10) cytotoxic furanosesterterpenes were isolated from a marine sponge Psammocinia sp. by bioactivity-guided fractionation. The structures were established on the basis of NMR and MS analyses. The geometry and absolute configuration were determined on the basis of optical rotation, NMR, and CD data. These compounds were evaluated for cytotoxicity against a small panel of five human tumor cell lines, and most of the compounds showed toxicity to SK-MEL-2. The mixture of compounds 7 and 8 displayed significant inhibition of DNA replication and moderate antioxidant profile.

Animals↗
PubMed2004

Gene expression analysis of the pro-oestrous-stage rat uterus reveals neuroligin 2 as a novel steroid-regulated gene.

In the present study, differential gene expression in the uteri of ovariectomised (OVX) and pro-oestrous rats (OVX v. pro-oestrus pair) was investigated using cDNA expression array analysis. Differential uterine gene expression in OVX rats and progesterone (P(4))-injected OVX rats (OVX v. OVX + P(4) pair) was also examined. The uterine gene expression profiles of these two sets of animals were also compared for the effects of P(4) treatment. RNA samples were extracted from uterine tissues and reverse transcribed in the presence of [alpha(32)P]-dATP. Membrane sets of rat arrays were hybridised with cDNA probe sets. Northern blot analysis was used to validate the relative gene expression patterns obtained from the cDNA array. Of the 1176 cDNAs examined, 23 genes showed significant (>two-fold) changes in expression in the OVX v. pro-oestrus pair. Twenty of these genes were upregulated during pro-oestrus compared with their expression in the OVX rat uterus. In the OVX v. OVX + P(4) pair, 22 genes showed significant (>two-fold) changes in gene expression. Twenty of these genes were upregulated in the OVX + P(4) animals. The genes for nuclear factor I-XI, afadin, neuroligin 2, semaphorin Z, calpain 4, cyclase-associated protein homologue, thymosin beta-4X and p8 were significantly upregulated in the uteri of the pro-oestrus and OVX + P(4) rats of both experimental pairs compared with the OVX rat uteri. These genes appear to be under the control of P(4). One of the most interesting findings of the present study is the unexpected and marked expression of the neuroligin 2 gene in the rat uterus. This gene is expressed at high levels in the central nervous system and acts as a nerve cell adhesion factor. According to Northern blot analysis, neuroligin 2 gene expression was higher during the pro-oestrus and metoestrus stages than during the oestrus and dioestrus stages of the oestrous cycle. In addition, neuroligin 2 mRNA levels were increased by both 17beta-oestradiol (E(2)) and P(4), although P(4) administration upregulated gene expression to a greater extent than injection of E(2). These results indicate that neuroligin 2 gene expression in the rat uterus is under the control of both E(2) and P(4), which are secreted periodically during the oestrous cycle.

Animals↗
PubMed2003

New bromotyrosine derivatives from an association of two sponges, Jaspis wondoensis and Poecillastra wondoensis.

Three new bromotyrosine derivatives (4-6) were isolated from an association of two sponges, Jaspis wondoensis and Poecillastra wondoensis, along with the previously described (E,E)-psammaplin A (1), (E,Z)-psammaplin A (2), psammaplin D (3), bisaprasin (7), and (3-bromo-4-hydroxyphenyl)acetonitrile (8). The structures of the new compounds were established on the basis of NMR and MS spectroscopic analysis. The compounds 1, 3, and 5-7 displayed significant cytotoxicity against human lung (A549), ovarian (SK-OV-3), skin (SK-MEL-2), CNS (XF498), and colon (HCT15) cancer cell lines. Compounds 3-7 were further evaluated for antibacterial activity against methicillin- or ofloxacin-resistant Staphylococcus strains. Compound 4 exhibited more potent antibacterial activity than meropenem against several strains.

Animals↗