• Journal of the Korean Chemical Society
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• v.41 no.7
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• pp.357-361
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• 1997

8-Azaxanthine (1), 3-${\beta}$-D-ribofuranosyl-8-azaxanthine (2), 3-${\beta}$-D-ribofuranosyl-8-azaxanthine-5'-monophosphate (3), and 3-${\beta}$-D-ribofuranosyl-8-azaxanthine-5'-(3-pyridinylcarbonyl)monophosphate (4) were synthesized. The in vitro antitumor activities of the synthesized compounds against P388 mouse leukemia, FM3A mammary carcinoma, and U937 human histiocytic lymphoma cells were determined by MTT assay. 2 with unnatural N-3 and C-1' glycoside bond had activity against three tumor cell lines and $IC_{50}$s of these compounds were 0.05, 0.06, and 0.06 ${\mu}mol/mL$ against three tumor cell lines, respectively. But these compounds had no antibacterial activity. $IC_{50}$s against U937 human histiocytic lymphoma cells were verified with the structural modification: $IC_{50}$s of 1, 2, 3, and 4 were 0.33, 0.06, 0.25, and 0.33 ${\mu}mol/mL$, respectively.

• Journal of Life Science
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• v.30 no.4
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• pp.379-385
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• 2020

Phlojodicarpus sibiricus and Artemisia kruhsiana Besser are medicinal plants traditionally used in Russia. Phlojodicarpus sibiricus extracts (PSE) have been shown to have anti-obesity properties, and Artemisia kruhsiana Besser extracts (AKBE) contain terpenoid compounds that exert various medicinal effects. Here, we investigated the potential pro-apoptotic effects of PSE and AKBE in diffuse large B-cell lymphoma (DLBCL) and elucidated the underlying mechanism. PSE and AKBE treatment of six DLBCL cell lines with various genetic abnormalities effectively reduced cell viability in a dose-dependent manner, while having a minimal impact on the survival of normal murine bone marrow cells and splenocytes. This suggests that the cytotoxic effects of PSE and AKBE are specific to DLBCL cells. Therefore, we expect limited side effects when these plant extracts are administered to DLBCL patients. Our JC-1 assays demonstrate that the pro-apoptotic effects of these plant extracts are produced by a reduction of anti-apoptotic Bcl-2 family members and, thereby, disruption of the mitochondrial membrane potential. Moreover, PSE and AKBE induce cell death independently of Myc, whose abnormalities are frequently observed in patients with DLBCL and are associated with poor prognosis. Our findings reveal hitherto uncharacterized pro-apoptotic effects of PSE and AKBE in DLBCL. Isolation of single compounds with anti-lymphoma activities should be pursued further.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.62-66
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• 2016

Amygdalin, D-mandelonitrile-${\beta}$-D-glucoside-6-${\beta}$-glucoside, belongs to aromatic cyanogenic glycoside group derived from rosaceous plant seed. Mounting evidence has supported the anti-cancer effects of amygdalin. However, whether amygdalin indeed acts as an anti-tumor agent against breast cancer cells is not clear. The present study aimed to investigate the effect of amygdalin on the proliferation of human breast cancer cells. Here, we show that amygdalin exerted cytotoxic activities on estrogen receptors (ER)-positive MCF7 cells, and MDA-MB-231 and Hs578T triple-negative breast cancer (TNBC) cells. Amygdalin induced apoptosis of Hs578T TNBC cells. Amygdalin downregulated B-cell lymphoma 2 (Bcl-2), upregulated Bcl-2-associated X protein (Bax), activated of caspase-3 and cleaved poly ADP-ribose polymerase (PARP). Amygdalin activated a pro-apoptotic signaling molecule p38 mitogen-activated protein kinases (p38 MAPK) in Hs578T cells. Treatment of amygdalin significantly inhibited the adhesion of Hs578T cells, in which integrin ${\alpha}5$ may be involved. Taken together, this study demonstrates that amygdalin induces apoptosis and inhibits adhesion of breast cancer cells. The results suggest a potential application of amygdalin as a chemopreventive agent to prevent or alleviate progression of breast cancer, especially TNBC.

• The Korean Journal of Cytopathology
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• v.6 no.2
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• pp.116-124
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• 1995

Eighty cases of malignant effusion were cytologically studied to elucidate the incidence of primary tumor site and cytologic characteristics of each tumor types. Eighty fluid specimens were composed of 43 ascitic, 35 pleural, and 2 pericardial effusion and primary tumor site had been confirmed by histology. The frequent primary sites were stomach(22 cases, 28%), lung(21 cases, 26%), ovary(11 cases, 14%), liver(7 cases, 9%), and breast (4 cases, 5%). The principal malignant tumors were adenocarcinoma (56 cases, 70%), squamous cell carcinoma (7 cases, 9%), liver cell carcinoma (7 cases, 9%), small cell carcinoma (4 cases, 5%), and non-Hodgkin's lymphoma (4 cases, 5%). The distinctive cytologic findings according to primary tumor types were as follows; the gastric adenocarcinomas were mainly characterized by isolated cells and irregular clusters sometimes with signet ring cells. Papillary serous cystadenocarcinoma of ovary showed frequently papillary clusters and occasional psammoma bodies. Breast carcinoma of ductal type showed cell balls with smooth margins. Colonic adenocarcinoma showed rather irregular clusters or palisading pattern of cylindrical cells. Metastatic squamous cell carcinoma, liver cell carcinoma, small cell carcinoma, and non-Hodgkln's lymphoma showed also characteristic features. These findings Indicate that the cytological features observed in the great majority of malignant effusion are similar to those of primary tumor types, which are very helpful to indentify the primary tumor site.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.51-55
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• 2016

Phytochemical investigation of Pistacia integerrima has highlighted isolation of two known compounds naringenin (1) and dihydrokaempferol (2). A crude extract and these isolated compounds were here evaluated for their effects on reversion of multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). The multidrug resistance P-glycoprotein is a target for chemotherapeutic drugs from cancer cells. In the present study rhodamine-123 exclusion screening test on human mdr1 gene transfected mouse gene transfected L5178 and L5178Y mouse T-cell lymphoma cells showed excellent MDR reversing effects in a dose dependent manner. In-silico molecular docking investigations demonstrated a common binding site for Rhodamine123, and compounds naringenin and dihydrokaempferol. Our results showed that the relative docking energies estimated by docking softwares were in satisfactory correlation with the experimental activities. Preliminary interaction profile of P-gp docked complexes were also analysed in order to understand the nature of binding modes of these compounds. Our computational investigation suggested that the compounds interactions with the hydrophobic pocket of P-gp are mainly related to the inhibitory activity. Moreover this study s a platform for the discovery of novel natural compounds from herbal origin, as inhibitor molecules against the P-glycoprotein for the treatment of cancer.

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.151-158
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• 2006

Khal was a synthetic congener of halocidin, a heterodimeric peptide consisting of 19 and 15 amino acid residues detected in Halocynthia aurantium. This compound was considered a candidate for the development of a novel peptide antibiotic. The genotoxicity of Khal was subjected to high throughput toxicity screening (HTTS) because they revealed strong antibacterial effects. Mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), single cell gel electrophoresis (Comet) assay and chromosomal aberration assay in mammalian cells and Ames reverse mutation assay in bacterial system were used as simplified, inexpensive, short-term in vitro screening tests in our laboratory. These compounds are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. Before performing the comet assay, $IC_{20}$ of Khal was determined the concentration of $25.51\;{\mu}/mL\;and\;21.99\;{\mu}g/mL$ with and without S-9, respectively. In the comet assay, Khal was not induced DNA damage in mouse lymphoma cell line. Also, the mutation frequencies in the Khal-treated cultures were similar to the vehicle controls. It is suggests that Khal is non-mutagenic in MOLY assay. And no clastogenicity was observed in Khal-treated Chinese hamster lung cells. The results of this battery of assays indicate that Khal has no genotoxic potential in bacterial or mammalian cell systems. Therefore, we suggest that Khal, as the optimal candidates with both no genotoxic potential and antibacterial effects must be chosen.

• The Journal of Korean Obstetrics and Gynecology
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• v.35 no.3
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• pp.1-23
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• 2022

Objectives: The purpose of this study is to evaluate anti-breast cancer and anti-inflammatory effects of Chungganhaewool-tang and Shipyeukmiyeugi-eum. Methods: MDA-MB-231 cells were used to measure cytotoxicity, Reactive oxygen species (ROS) production, protein expression amounts of Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xl), Cytochrome C Caspase-3, Caspase-7, Caspase-9, Poly ADP-ribose polymerase (PARP), Nuclear factor erythroid-2-related factor 2 (Nrf2), Heme oxygenase-1 (HO-1) and NAD (P) H Quinone Oxidoreductase 1 (NQO1) to evaluate the anti-breast cancer effects of Chungganhaewool-tang (CHT) and Shipyeukmiyeugi-eum (SYE), and THP-1 cells, differentiated into macrophage and induced inflammation with Lipopolysaccharide (LPS), were used to measure production amounts of ROS, Nitric oxide (NO), and protein expression amounts of Inducible nitric oxide synthase (iNOS), Cyclooxygenase (COX-2), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-α) to evaluate the anti-inflammatory effects of CHT and SYE. Results: CHT and SYE reduced MDA-MB-231 cell counts, increased protein expression of Bax and Cytochrome C, and decreased protein expression of Bcl-2, Bcl-xl. The protein expression amounts of Caspase-3, 7, and 9 decreased, but amounts of the active form, cleaved Caspase-3, 7, and 9, increased. In addition, PARP protein expression decreased, the amount of PARP protein in the cleaved form increased, and the amount of protein expressions of Nrf2 and HO-1 decreased, but NQO1 showed no significant difference. In THP-1 cells CHT and SYE reduced ROS and NO, and reduced protein expressions of iNOS, COX-2, IL-1, and TNF-α, but only SYE groups reduced IL-6. Conclusions: This study suggests that CHT and SYE have potential to be used as treatments for breast cancer.

• BMB Reports
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• v.49 no.4
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• pp.226-231
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• 2016

Epstein Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1) plays a pivotal in an EBV episome replication and persistence. Despite considerable attempts, there are no EBV drugs or vaccines. We attempted to eradicate EBV episomes by targeting EBNA1 using the transcription activator-like effector nucleases (TALEN) (E1TN). E1TN-mediated transient knockout (KO) of EBNA1 reduced EBNA1 expression, and caused significant loss of EBV genomes and progressive death of EBV-infected cells. Furthermore, when a mixture of EBV-infected Burkitt's lymphoma (BL) cells and EBV-negative BL cells was targeted by E1TN, EBV-negative cells were counter-selected while most EBV-infected cells died, further substantiating that EBNA1 KO caused selective death of EBV-infected cells. TALEN-mediated transient targeting of EBNA1 attenuated the growth of EBV-infected cells, implicating a possible therapeutic application of E1TN for EBV-associated disorders.

• Korean Journal of Veterinary Research
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• v.62 no.3
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• pp.20.1-20.8
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• 2022

5-Fluorouracil, doxorubicin, and vincristine are chemotherapy agents used to treat various cancers, such as breast cancer and lymphoma for decades, and their effects on cancer have been proven. On the other hand, these anti-cancer drugs cause fatal side effects, including immunosuppression. This study investigated whether sonicated Bordetella bronchiseptica bacterin (B. bronchiseptica) can attenuate the immunosuppression of spleen cells induced by these chemotherapy agents and which subsets of spleen cells were affected. B. bronchiseptica increased the metabolic activity of spleen cells treated with 3 anti-cancer drugs. Cell death analysis using Annexin V/propidium iodide showed that B. bronchiseptica markedly decreased the death of spleen cells. The subsets of spleen cells were analyzed by flow cytometry using a surface marker-specific antibody. B. bronchiseptica increased nitric oxide production in the spleen cells treated with anti-cancer drugs (p < 0.0001). Despite the pharmacological effects of anti-cancer drugs, many patients suffer from the fatal side effects of immunosuppression. This study provides valuable information on how to overcome chemotherapy-induced immunosuppression.

• Korean Journal of Pharmacognosy
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• v.30 no.1
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• pp.7-11
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• 1999

The present work was carried out to examine the effect of costunolide on the growth of several cells and characteristics of U-937 human leukemia-derived cell line. Costunolide produced a potent antitumor activity in vitro dependent on concentration against several tumor cells such as P-388, L-1210 leukemia and SNU-5 stomach cancer cells. However, it showed less cytotoxicity on normal cells such as Maccaccus rheus monkey kidney cells (MA-104) up to 200 ${\mu}M$ concentration. An effect of cell differentiation by costunolide was assessed by its ability to reduce nitroblue tetrazolium (NBT), and to induce phagocytosis of latex particles. In order to establish whether costunolide induces U-937 cells to differentiate toward macrophage or granulocyte, esterase activities was measured. Based on these results, we found that costunolide having cytotoxicity on U-937 human leukemia cells was explained through differentiation inducing activity.