• 한국음향학회지
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• 제41권5호
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• pp.501-506
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• 2022

공학적으로 제작된 미소기포 중 가스층과 유체층을 함께 내포하는 echogenic liposome은 수용성 약물 탑재에 용이하다. 또한 특정 위치에서 약물을 방출할 수 있다는 점에서 초음파 조영제의 기능을 넘어서 초음파 기반 약물전달(sonoporation)에 활용될 수 있다. 이에 따라, 본 논문에서는 이전 연구에서 제안된 echogenic liposome의 구조를 EF-TEM으로 재확인하였으며 sonoporation에서 약물전달 매개체로의 효과를 세포실험을 통하여 입증하였다. 세포실험은 유방암 조직인 MDA-MB-231 세포 대상으로 대표적 암치료제인 Doxorubicin을 지표 약물로 활용하였다. 비교군(1 그룹), Doxorubicin 그룹(2 그룹), Doxorubicin 과 일반 기포를 추가하여 sonoporation을 한 그룹(3 그룹), Doxorubicin을 echogenic liposome에 탑재하여 sonoporation을 적용한 그룹(4 그룹)으로 구분하여 진행한 실험결과, 4 그룹에서 약물 전달 효과가 초기부터 급격히 증가하였으며, 최종적으로 2 그룹과 3그룹에 비하여 최소 1.4 배 이상 효과적으로 종양 세포 괴사를 유도하였다. 따라서 sonoporation에서 echogenic liposome은 기존 일반적 미소기포보다 더 효율적인 약물 매개체라고 결론 내릴 수 있다.

• 한국환경성돌연변이발암원학회지
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• 제26권1호
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• pp.12-19
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• 2006

Cadmium, a human carcinogen, can induce toxicity in various cell lines and organs. Despite extensive research, the mechanisms of cadmium-induced cell toxicity and estrogenic potential in human are not clear. This study was performed to investigate cadmium-induced toxicity on human breast cancer cells: MCF-7 cells, an estrogen receptor (ER) positive breast cancer cells, and MDA-MB-231 cells, an ER negative breast cancer cells. MCF-7 cells was proved to be more sensitive than the other cell lines (IC50 = $50\;{\mu}M$ at MCF-7 cells and $120{\mu}M$ at MDA-MB-231). The expression of JNK and AP-1 transcription factors such as c-Jun and c-Fos dependent transcription were increased by cadmium treatment. Inhibition of ER activation by ER antagonist (tamoxifen or ICI 182,780) significantly recovered the viablity and inhibited apoptotic cell death. This suggested that cadmium-induced cell death in ER (+) cells was mediated by JNK/AP-1 pathway and this pathway was more stimulated by ER activated by cadmium. Co-treatment of antioxidants such as selenium (Se), butylated hydroxyanisole (BHA), glutathione (GSH), or N-acetyl-L-cysteine (NAC) recovered the cadmium-induced cell death in MCF-7 cells. Cadmium-induced lipid peroxidation was decreased by GSH, NAC, or BHA in MCF-7 cells. The expression of SOD protein was decreased by cadmium ($100{\mu}M$) but recovered by GSH, NAC, BHA, or Se. Our data showed that the cadmium-induced cell toxicity in human breast cancer cells could be protected by the antioxidants (Se, BHA, NAC, GSH, or NAC) and ER antagonist (tamoxifen or ICI 182,780). Therefore, toxicity of cadmium in breast cancer were mediated by oxidative stress and $ER{\alpha}$.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.107-107
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• 1997

Cytochrome P450 enzymes have been intensively investigated in hepatic tissues and several mammalian cell lines. Compared to most studies about cytochrome P450 isozymes in liver in vivo and hepatic, cell lines in vitro, the study of cytochrome P450IA1 in human breast cancer cells could be very important to understand the mechanism of the regulation of CYPIA1 gene expression and cell growth. MCF-7 human breast cancer cells are well characterized to study estrogen and antiestrogen action due to the fact that they contain high level of estrogen receptor and have biological markers characterized. And also MCF-7 cells express high level of arylhydrocarbon hydroxylase activity and human cytochrome P450IA1 cDNA was cloned from MCF-7 cells. Ah receptor was characterized in many breast cancer cell lines and polycyclic aromatic hydrocarbon such as 3-MC induced the expression of CYPIA1 gene and cytochrome P450- dependent monooxygenase activity. We undertook a study to examine the effect of estrogens and other chemicals on the regulation of human CYPIA1 gene expression in MCF-7 cells via RTPCR analysis, that might help us to understand the mechanism of the regulation of CYPIA1 gene expression and MCF-7 cell growth. Expression vector containing the functional 5'-regulatory region of human CYPIA1 fused to the CAT reporter gene was transfected into estrogen receptor positive MCF-T cells or estrogen receptor negative MDA-MB-231 cells. After these cells were treated with various chemicals, RTPCR was carried out to measure both CYPIA1 mRNA and CAT mRNA levels. 1nM 3-MC increased in both P450 and CAT mRNA levels over those of control by two folds in MCF-7 cells but does not in MDA-MB-231 cells. Estrogen or tamoxifen or retinoic acid or chrysin decreased in both P450 and CAT mRNA levels that were induced by 3-MC in MCF-7 when each chemical was administered with 3-MC concomitantly. These results suggested that the level of CYPIA1 gene expression is modulated with estrogen-related molecules and make it possible to speculate that ER is related to CYPIA1 gene expression and cell growth in breast cancer cells. [Supported by grants from the Korean Ministry of Education ]

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5797-5804
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• 2013

In order to enhance the bioavailability of curcumin its conjugates with piperic acid and glycine were synthesized by esterifying the 4 and 4' phenolic hydroxyls, the sites of metabolic conjugation. Antiproliferative and apoptotic efficacy of synthesized conjugates was investigated in MCF-7 and MDA-MB-231 cell lines. $IC_{50}$ values of di-O-glycinoyl (CDG) and di-O-piperoyl (CDP) esters of curcumin were found to be comparable with that of curcumin. Both conjugates induced chromatin condensation fragmentation and apoptotic body formation. CDP exposure to MCF-7 cells induced apoptosis initiating loss of mitochondrial membrane potential (${\Delta}{\Psi}m$) followed by inhibition of translocation of transcription factor NF-${\kappa}B$ and release of Cytochrome-C. Reactive oxygen species (ROS) production was evaluated by fluorescent activated cell sorter. Change in ratio of Bcl2/Bclxl was observed, suggesting permeablization of mitochondrial membrane leading to the release of AIF, Smac and other apoptogenic molecules. DNA fragmentation as a hallmark for apoptosis was monitored by TUNEL as well as agrose gel electrophoresis. Thus, it was proven that conjugation does not affect the therapeutic potential of parent molecule in vitro, while these could work in vivo as prodrugs with enhanced pharmacokinetic profile. Pharmacokinetics of these molecules under in vivo conditions is a further scope of this study.

• Journal of Ginseng Research
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• 제48권2호
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• pp.171-180
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• 2024

Background: Epimers of ginsenoside Rg3 (Rg3) have a low bioavailability and are prone to deglycosylation, which produces epimers of ginsenoside Rh2 (S-Rh2 and R-Rh2) and protopanaxadiol (S-PPD and R-PPD). The aim of this study was to compare the efficacy and potency of these molecules as anti-cancer agents. Methods: Crystal violet staining was used to study the anti-proliferatory action of the molecules on a human epithelial breast cancer cell line, MDA-MB-231, and human umbilical vein endothelial cells (HUVEC) and compare their potency. Cell death and cell cycle were studied using flow cytometry and mode of cell death was studied using live cell imaging. Anti-angiogenic effects of the drug were studied using loop formation assay. Molecular docking showed the interaction of these molecules with vascular endothelial growth factor receptor-2 (VEGFR2) and aquaporin (AQP) water channels. VEGF bioassay was used to study the interaction of Rh2 with VEGFR2, in vitro. Results: HUVEC was the more sensitive cell line to the anti-proliferative effects of S-Rh2, S-PPD and R-PPD. The molecules induced necroptosis/necrosis in MDA-MB-231 and apoptosis in HUVEC. S-Rh2 was the most potent inhibitor of loop formation. In silico molecular docking predicted a good binding score between Rh2 or PPD and the ATP-binding pocket of VEGFR2. VEGF bioassay showed that Rh2 was an allosteric modulator of VEGFR2. In addition, SRh2 and PPD had good binding scores with AQP1 and AQP5, both of which play roles in cell migration and proliferation. Conclusion: The combination of these molecules might be responsible for the anti-cancer effects observed by Rg3.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2765-2770
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• 2012

Background: There is a long standing interest in the identification of medicinal plants and derived natural products for developing cancer therapeutics. Here we investigated the antiproliferative properties of Melissa officinalis (MO) from Turkey on breast cancer. Methods: MO extracts were studied for cytotoxicity against breast cancer cell lines (MCF-7, MDA-MB-468 and MDA-MB-231). In vitro apoptosis studies were performed by annexin V staining and flow cytometry analyses. Immunohistochemistry for Ki-67 and caspase 7 in the tumoral tissue sections of DMBA-induced mammary tumors in rats was also performed, along with TUNEL assays to detect apoptotic cells. In vivo anticancer activity testing was carried out with reference to inhibition of growth of DMBA induced mammary tumors in rats. Results: MO showed cytotoxicity against three cancer cell lines, inducing increase in Annexin-positive cells. Expression of caspase-7 protein and TUNEL positive cells were much higher in rats treated by MO, compared with the untreated control group, while expression of Ki-67 was decreased. Furthermore, in vivo studies showed that mean tumor volume inhibition ratio in MO treated group was 40% compared with the untreated rats. Conclusion: These results indicated that MO extrcts have antitumoral potential against breast cancer.

• 한국자원식물학회지
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• 제32권5호
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• pp.442-447
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• 2019

이상의 연구 결과로 미루어 볼 때, 도깨비부채 잎(RPL)은 ${\beta}-catenin$의 분해 유도를 통해 대장암, 유방암, 폐암, 전립선암 및 췌장암 세포의 생육을 억제하는 것으로 나타났다. 본 결과는 도깨비부채 잎의 항암을 위한 대체보완소재 및 천연 항암제 개발을 위한 소재로 활용이 가능할 것으로 판단된다. 그러나 추가적 연구를 통해 도깨비 부채 잎의 항암 활성물질의 분석연구가 필요할 것으로 사료된다.

• BMB Reports
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• 제39권4호
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• pp.448-451
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• 2006

Chemopreventive and cytotoxic effect of genistein against human breast cancer cell lines was investigated. Genistein inhibited cell proliferation in estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) human breast carcinoma cell lines. Cytochrome P450 (CYP) 1A1-mediated ethoxyresorufin O-deethylase (EROD) activity was inhibited by genistein in a concentrationdependent manner. Genistein significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cyclooxy-genase-2 activity and protein expression at the concentrations of 10 (p < 0.05), 25 (p < 0.05) and 50 mM (p < 0.01). In addition, ornithine decarboxylase (ODC) activity was reduced to 53.8 % of the control after 6 h treatment with 50 mM genistein in MCF-7 breast cancer cells. These results suggest that genistein could be of therapeutic value in preventing human breast cancer.

• 산업기술연구
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• 제40권1호
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• pp.1-6
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• 2020

In the process of protein transcription and translation, various protein complexes bind to DNA, and all processes are precisely controlled. Among the proteins constituting this complex, a peptide derived from eukaryotic initiation factor (eIF) 2 was synthesized. In addition, in order to increase the efficiency of transduction of this peptide into cells, peptides with polyarginine, one of the protein transduction domains (PTD), were synthesized. Cell growth inhibition was confirmed in HER2 positive breast cancer (SK-Br-3) and HER2 negative breast cancer (MDA-MB-231), and cardiomyocytes (H9c2). The peptide with polyarginine had high transduction efficiency in all cells, and had excellent cancer cell growth inhibitory effects. The peptide used in this study might be useful peptide therapeutics for the treatment of cancer through future research.

• Natural Product Sciences
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• 제25권1호
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• pp.72-75
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• 2019

Bioassay-guided fractionation of the roots of Asarum sieboldii led to the isolation of the six compounds methylkakuol (1), sesamin (2), asarinin (3), xanthoxylol (4), and (2E,4E,8Z,10E/Z)-N-(2-methylpropyl) dodeca-2,4,8,10-tetraenamide (5/6). Among the isolates, xanthoxylol (4) exhibited significant cytotoxicity against human breast cancer cells MCF-7 and MDA-MB-231 in vitro with $IC_{50}$ values of 9.15 and $13.95{\mu}M$, respectively.