• Experimental and Molecular Medicine
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• v.51 no.2
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• pp.1.1-1.14
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• 2019

Hypoxia-inducible factor-$1{\alpha}$ ($HIF-1{\alpha}$) mediates tumor cell adaptation to hypoxic conditions and is a potentially important anticancer therapeutic target. We previously developed a method for synthesizing a benzofuran-based natural product, (R)-(-)-moracin-O, and obtained a novel potent analog, MO-460 that suppresses the accumulation of $HIF-1{\alpha}$ in Hep3B cells. However, the molecular target and underlying mechanism of action of MO-460 remained unclear. In the current study, we identified heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) as a molecular target of MO-460. MO-460 inhibits the initiation of $HIF-1{\alpha}$ translation by binding to the C-terminal glycinerich domain of hnRNPA2B1 and inhibiting its subsequent binding to the 3'-untranslated region of $HIF-1{\alpha}$ mRNA. Moreover, MO-460 suppresses $HIF-1{\alpha}$ protein synthesis under hypoxic conditions and induces the accumulation of stress granules. The data provided here suggest that hnRNPA2B1 serves as a crucial molecular target in hypoxiainduced tumor survival and thus offer an avenue for the development of novel anticancer therapies.

• BMB Reports
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• v.52 no.5
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• pp.342-347
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• 2019

Methylation is a primary epigenetic mechanism regulating gene expression. 5-aza-2'-deoxycytidine is an FDA-approved drug prescribed for treatment of cancer by inhibiting DNA-Methyl-Transferase 1 (DNMT1). Results of this study suggest that prolonged treatment with 5-aza-2'-deoxycytidine could induce centrosome abnormalities in cancer cells and that CEP131, a centrosome protein, is regulated by DNMT1. Interestingly, cancer cell growth was attenuated in vitro and in vivo by inhibiting the expression of Cep131. Finally, Cep131-deficient cells were more sensitive to treatment with DNMT1 inhibitors. These findings suggest that Cep131 is a potential novel anti-cancer target. Agents that can inhibit this protein may be useful alone or in combination with DNMT1 inhibitors to treat cancer.

• Molecules and Cells
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• v.40 no.6
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• pp.401-409
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• 2017

The primary cilium is a non-motile microtubule-based organelle that protrudes from the surface of most human cells and works as a cellular antenna to accept extracellular signals. Primary cilia assemble from the basal body during the resting stage ($G_0$ phase) and simultaneously disassemble with cell cycle re-entry. Defective control of assembly or disassembly causes diverse human diseases including ciliopathy and cancer. To identify the effective compounds for studying primary cilium disassembly, we have screened 297 natural compounds and identified 18 and 17 primary cilium assembly and disassembly inhibitors, respectively. Among them, the application of KY-0120, identified as Brefeldin A, disturbed Dvl2-Plk1-mediated cilium disassembly via repression of the interaction of $CK1{\varepsilon}-Dvl2$ and the expression of Plk1 mRNA. Therefore, our study may suggest useful compounds for studying the cellular mechanism of primary cilium disassembly to prevent ciliopathy and cancer.

• Microbiology and Biotechnology Letters
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• v.22 no.4
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• pp.347-352
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• 1994

Cytotoxic test was performed by SRB assay on human epidermoid carcinoma HEp-2 cell line for screening the soil microorganism, secreting anticancer agent. One microorganism was selected among two thousand microorganisms for its highest cytotoxicity. And this microorganism was identified with Streptomyces species after performing of diaminopimeric acid and reducing sugar analysis of cell wall and analysing the cultural characteristics and named Streptomyces sp. SM 1119. The effect of anticancer agent in SM 1119 culture extract on the cell cycle was studied by using GG$_{o}$ synchronized NIH 3T3 cells. The extract inhibited the serum stimulation of GG$_{o}$ NIH 3T3 cell only within 1 hour after serum stimulation but not after 6 hours. The extract also reduced the amount of c-myc mRNA in Colo 320 cell. These results suggest that the anticancer agent in the extract inhibits the progression of cell cycle very early stages, probably from G$_{0}$ to G$_{1}$.

• Journal of Microbiology and Biotechnology
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• v.31 no.12
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• pp.1667-1671
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• 2021

A new homocysteine thiolactone derivative, thiolactomide (1), was isolated along with a known compound, N-acetyl homocysteine thiolactone (2), from a culture extract of soil-derived Streptomyces sp. RK88-1441. The structures of these compounds were elucidated by detailed NMR and MS spectroscopic analyses with literature study. In addition, biological evaluation studies revealed that compounds 1 and 2 both exert neuroprotective activity against 6-hydroxydopamine (6-OHDA)-mediated neurotoxicity by blocking the generation of hydrogen peroxide in neuroblastoma SH-SY5Y cells.

• Archives of Pharmacal Research
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• v.24 no.5
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• pp.397-401
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• 2001

In the search for new naturally occurring angiogenic inhibitory we found that culture broths from two unidentified fungal strains exerted potent inhibitory activities on capillary-like tube formation of human umbilical vein endothelial cells (HUVEC) in vitro. Two active compounds were isolated by bioassay-guided separation and their structures were identified as gliotoxin (1) and its derivative methylthiogliotoxin (2) by spectroscopic analyses. These compounds significantly inhibited the migration of HUVEC assessed by in vitro wounding migration assay and exhibited at least 10 times more potent inhibition of proliferation of HUVECs as compared with that of cancer cell lines such as HeLa, MCF-7, and KB 3-1 cells. Especially, gliotoxin having disulfide group exerted more potent activities than methylthiogliotoxin, suggesting that gliotoxin could be a useful compound for further study as an anti-angiogenic agent.

• Journal of Microbiology and Biotechnology
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• v.32 no.3
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• pp.302-306
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• 2022

A chemical investigation of a culture extract from Streptomyces sp. RK85-270 led to the isolation and characterization of two new oxindoles, RK-270D (1) and E (2). The structures of 1 and 2 were determined by analyzing spectroscopic and spectrometric data from 1D and 2D NMR and High-resolution electrospray ionization mass spectrometry (HRESIMS) experiments. Compound 1 exhibited anti-angiogenic activities against human umbilical vein endothelial cells (HUVECs) without cytotoxicity. Results of Western blot analysis revealed that 1 inhibits VEGF-induced angiogenesis in the HUVECs via VEGFR2/ p38 MAPK-mediated pathway.

• Microbiology and Biotechnology Letters
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• v.41 no.3
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• pp.379-382
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• 2013

In order to investigate the anticancer activity of an anti-yeast substance (AYS), a proteoglycan produced by Rhanella aquatilis AY2000, the cytotoxicity of the AYS against cancer cells was determined in vitro. The AYS was not cytotoxic to the human Jurkat T cell or the mouse sarcoma 180 cell, but was cytotoxic to the human colon cancer TH20 cell. The AYS was increasingly cytotoxic against human colon cancer cells in a dose-dependent manner at range from 62.5 to 500 ${\mu}g/ml$. Anticancer activity by combination of the AYS and an anticancer agent was also determined. The anticancer agent combined with the AYS was shown to possess greater synergistic anticancer activity against human colon cancer cells, as compared with the anticancer agent alone.

• Journal of Microbiology and Biotechnology
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• v.30 no.1
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• pp.31-37
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• 2020

We previously identified a new heparinase inhibitor fungal metabolite, named CRM646-A, which showed inhibition of heparinase and telomerase activities in an in vitro enzyme assay and antimetastatic activity in a cell-based assay. In this study, we elucidated the mechanism by which CRM646-A rapidly induced nucleus condensation, plasma membrane disruption and morphological changes by increasing intracellular Ca²⁺ levels. Furthermore, PD98059, a mitogen-activated protein kinase (MEK) inhibitor, inhibited CRM646-A-induced nucleus condensation through ERK1/2 activation in rat 3Y1 fibroblast cells. We identified CRM646-A as a Ca²⁺ ionophore-like agent with a distinctly different chemical structure from that of previously reported Ca²⁺ ionophores. These results indicate that CRM646-A has the potential to be used as a new and effective antimetastatic drug.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.11a
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• pp.122-122
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• 2004