• 한국환경성돌연변이발암원학회지
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• 제25권1호
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• pp.40-46
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• 2005

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although the mechanism of carcinogenesis by TCDD is unclear, it is considered to be a non-genotoxic compound and tumor promoter. In our experiment, we investigated the effects of TCDD on gene expression in mouse skin carcinogenesis. We used cDNA microarray to detect the differential gene expression in tumors induced in hairless mouse skin by MNNG plus TCDD protocol. We found that erb-2, c-ets2 and p27$^{kip1}$ were significantly up-regulated, but TNFR2, AKT-l, integrin $\beta$l, maspin, IGF-l, c-raf-l, Rb were significantly down-regulated, in tumor region, respectively. We also found that the expression of 53 genes involved in cen cycle, signal transduction, apoptosis, adhesion molecule, angiogenesis, and invasion, were changed two fold more, in tumor surrounding region. These data suggest that TCDD alters the expression of a large array of genes involved in apoptosis, cytokine production and angiogenesis in mouse skin carcinogenesis.

• Journal of Periodontal and Implant Science
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• 제30권4호
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• pp.869-885
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• 2000

Fibroblasts are major cellular components of gingiva and periodontal ligament. They regulate the healing process after surgery or injury. Recently, many natural medicines, whose advantages are less side effects and possibility of long-term use, have been studied for their capacity, their anti-bacterial and anti-inflammatory effects and regenerative potential of periodontal tissues. Sophorae radix have been traditionally used as an anti-bacterial and antiinflammatory drug in oriental medicine. The purpose of present study was to investigate the effects of Sophorae radix extract on cell cycle progression and its molecular mechanism in human gingival fibroblasts. Sophorae radix extracts($100{\mu}g/ml$) notably increased cell proliferation and cell activity in the human gingival fibroblasts as compared to non-supplemented controls. There was an increase in the S phase and a decrease in the G1 phase in $100{\mu}g/ml$ of Sophorae radix extracts group as compared to non-supplemented controls. The level of cyclin E and cdk 2 protein in test group was higher than that of control groups. But that of cyclin D, cdk 4, and cdk 6 was not distinguished from controls. The level of p53 protein in test group was lower than that of controls, whereas that of p21 was not different. The level of pRB protein in test group was higher than that of controls, whereas that of p16 was lower. These results indicate that the increase of cell proliferation by Sophorae radix extracts may be due to the increased expression of cyclin E and cdk 2, and the decreased expression of p53 and p16 in human gingival fibroblasts.

• Journal of Periodontal and Implant Science
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• 제35권1호
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• pp.87-98
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• 2005

The purpose of present study was to investigate the effects of physiologically active compound (SD62-122) from Phlomidis Radix on the cell cycle progression and its molecular mechanism in human gingival fibroblasts(HGFs). For this purpose, fibroblasts were isolated and cultured from excisioned gingiva during crown lengthening procedure in healthy adult. The following parameter were evaluated that there are cell number counting, MIT assay, cell cycle progression, western blot analysis. The cell number and MIT assay of primary cultured fibroblast was not increased at 2 days but significant increased compare to negative control at 3days(p<0.05). S phase was increased and G1 phase decreased in both $10^{-8}M$ and $10^{-9}M$ of SD62-122 in cell cycle analysis. The cell cycle regulation protein levels of Cyclin $D_1$, Cyclin E, cdk 2, cdk 4 and cdk 6 were increased compare to control in both $10^{-8}M$ and $10^{-9}M$ of SD62-122. The protein levels of p21 and p53 were decreased compare to control, but the level of pRb was not changed compare to control in $10^{-9}M$ of SD2-122. These results suggested that physiologically active compound (SD62-122) isolated from Phlomidis Radix increases the cell proliferation and cell cycle progression in HGFs, which is linked to increased cell cycle regulation protein levels of Cyclin $D_1$, Cyclin E, cdk 2, cdk 4 and cdk 6, and decreased the levels of p21, p53.

• 약학회지
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• 제48권6호
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• pp.328-334
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• 2004

Cervical cancer is one of the leading causes of female death. Viral oncoproteins E6 and E7 are selectively retained and expressed in carcinoma cells infected with HPV (Human pa pilloma virus) type 16 and cooperated in immotalization and transformation of primary keratinocyte. E6 and E7 oncoproteins interfere the functions of tumor suppressor proteins p53 and retinoblasoma protein (pRb), respectively. Among a lots of natural products, Mentha arvensis Linne var.piperascens have inhibitory effects on bindings between E6 oncoprotein and tumor suppressor p53, E3 ubiqutin- protein ligase (E6AP). HPV oncoprotein inhibitors from Mentha piperita L. were isolated by solvent partition and column chromatography (Silica gel, RP-18) and inhibitory compounds were finally purified by HPLC using an ELISA screening system based on binding between E6 and E6AP. The aim of this study is to identify the structure of inhibitory compounds and to investigate whether these compounds have inhibitory effects on functions of E6 oncoprotein. We investigated whether caffeic acid methyl ester (CAM) extracted from Mentha piperita L. could inhibit the function of E6 oncoprotein. CAM inhibited the in vitro binding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53 and also inhibited the proliferation of human cervical cancer cell lines (SiHa and CaSKi) in a dose response manner. These results suggest that CAM inhibited the function of E6 oncoprotein, suggesting that it can be used as a potential drug for the treatment of cervical cancers infected with HPV.

• 방사선산업학회지
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• 제6권3호
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• pp.223-229
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• 2012

In this study, we investigated the biological damage and stress responses induced by ion beam (proton beam) irradiation as a basis for the development of protective measures against space radiation. We examined the biological effects of proton beam produced by MC-50 cyclotron at KIRAMS on the cultured cells and mice. The proton beam energy used in this study was 34.9 MeV and the absorption dose rate for cells and mice were $0.509Gy\;sec^{-1}$ and $0.65Gy\;sec^{-1}$, respectively. The cell survival rates measured by plating efficiency showed the different sensitivity and dose-relationship between CHO cells and Balb/3T3 cells. HGPRT gene mutation frequency in Balb/3T3 was $15{\times}10^{-6}Gy^{-1}$, which was similar to the reported value of X-ray. When stress signaling proteins were examined in Balb/3T3 cells, $I{\kappa}B-{\alpha}$ decreased markedly whereas p53, phospho-p53, and Rb increased after proton beam irradiation, which implied that the stress signaling pathways were activated by proton beam irradiation. In addition, cellular senescence was induced in IMR-90 cells. In the experiments with C57BL/6 mouse, the immune cells (white blood cells, lymphocytes) in the peripheral blood were greatly reduced following proton beam irradiation whereas red blood cells and platelets showed relatively little change. These results can be utilized as basic data for studying the biological effects of proton beam using MC-50 cyclotron with respect to proton therapy research as well as space radiation research.

• 한국식품과학회지
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• 제32권6호
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• pp.1389-1395
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• 2000

자궁 경부암은 매년 약 50만명 정도씩 사망하는 여성의 치명적인 사망원인의 하나이다. 인두유종 바이러스(HPV) 16형 및 18형과 자궁 경부암과의 긴밀한 관련성은 잘 알려져 있다. 옻 추출물 Rhus가 HPV 16형의 E6, E7 발암 유전자를 억제하는지 여부를 측정하였다. 이 Rhus는 자궁 경부암 세포주(C-33A, SiHa, Caski)와 HaCaT keratinocytes의 분열은 농도 의존적으로 억제하였다. In vitro binding assay와 효소면역측정법에 의하면 Rhus가 암 억제인자인 p53과 결합하여 분해 시키는데 필수적인 E6와 E6AP와의 결합을 억제할 뿐더러 암 억제인자 Rb와 E7과의 결합을 억제하였다. RT-PCR에 의하면 Rhus에 의해 E6 mRNA의 level이 감소하였으나 E7 mRNA는 변하지 않았음을 보여주었다. 이들 결과에 의하면 Rhus가 HPV 16형의 E6와 E7의 발암성을 억제함을 보여 주므로 HPV에 의해 유도된 자궁 경부암의 치료에 유효할 것으로 사료되어 좀 더 자세한 in vitro실험 등이 요구된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6967-6972
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• 2015

Background: Cigarette smoking and tobacco chewing are common modes of consuming tobacco all over the world. Parents need to be aware that germ cell integrity is vital for birth of healthy offspring as biological parenting begins much before birth of a child and even before conception. The present study was conducted to determine the etiology of non-familial sporadic heritable retinoblastoma (NFSHRb), by evaluating oxidative sperm DNA damage in fathers due to use of tobacco (smoking and chewing). Materials and Methods: We recruited 145 fathers of NFSHRb children and 53 fathers of healthy children (controls) in the study. Tobacco history was obtained by personal interview. Seminal reactive oxygen species (ROS) in semen, sperm DNA fragmentation index (DFI) and 8 hydroxy 2' deoxyguanosine (8-OHdG) levels in sperm were evaluated. The RB1 gene was screened in genomic blood DNA of parents of children with NFSHRb and controls. Odds ratios (ORs) derived from conditional logistic regression models. Results: There was significant difference in the levels of ROS (p<0.05), DFI (p<0.05) and 8-OHdG (p<0.05) between tobacco users and non-users. The OR of NFSHRb for smokers was 7.29 (95%CI 2.9-34.5, p<0.01), for tobacco chewers 4.75 (2.07-10.9, p<0.05) and for both 9.11 (3.79-39.2; p<0.01). Conclusions: This study emphasizes the adverse effect of tobacco on the paternal genome and how accumulation of oxidative damage in sperm DNA may contribute to the etiology of NFSHRb. In an ongoing parallel study in our laboratory, 11 of fathers who smoked underwent. Meditation and yoga interventions, showed significant decline in levels of highly mutagenic oxidised DNA adducts after 6 months. Thus our lifestyle and social habits impact sperm DNA integrity and simple interventions like yoga and meditation are therapeutic for oxidative damage to sperm DNA.

• BMB Reports
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• 제48권8호
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• pp.454-460
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• 2015

Naturally occurring reoviruses are live replication-proficient viruses that specifically infect human cancer cells while sparing their normal counterpart. Since the discovery of reoviruses in 1950s, they have shown various degrees of safety and efficacy in pre-clinical or clinical applications for human anti-cancer therapeutics. I have recently discovered that cellular tumor suppressor genes are also important in determining reoviral tropism. Carcinogenesis is a multi-step process involving the accumulation of both oncogene and tumor suppressor gene abnormalities. Reoviruses can exploit abnormal cellular tumor suppressor signaling for their oncolytic specificity and efficacy. Many tumor suppressor genes such as p53, ataxia telangiectasia mutated (ATM), and retinoblastoma associated (RB) are known to play important roles in genomic fidelity/maintenance. Thus, a tumor suppressor gene abnormality could affect host genomic integrity and likely disrupt intact antiviral networks due to the accumulation of genetic defects which in turn could result in oncolytic reovirus susceptibility. This review outlines the discovery of oncolytic reovirus strains, recent progresses in elucidating the molecular connection between oncogene/tumor suppressor gene abnormalities and reoviral oncotropism, and their clinical implications. Future directions in the utility of reovirus virotherapy is also proposed in this review. [BMB Reports 2015; 48(8): 454-460]

• 대한의생명과학회지
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• 제28권2호
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• pp.92-100
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• 2022

Ginkgo biloba Leaf Extract (GBE) is an extract from leaves of the Ginkgo biloba tree, widely used as a health supplement. GBE can inhibit the proliferation of several types of tumor cell. Although it is known to have anti-cancer effects in breast cancer and skin cancer, research related to gastric cancer is still insufficient. Based on results showing anti-cancer effects on solid cancer, we aimed to determine whether GBE has similar effects on gastric cancer. In this study, the anti-cancer effect of GBE in gastric adenocarcinoma was investigated by confirming the cell proliferation inhibitory effect of AGS cells. We also evaluated whether GBE regulates expression of the tumor suppressor protein p53 and Rb. GBE has apoptotic effects on AGS cells that were confirmed by changes in anti-apoptosis protein Bcl-2, Bcl-xl and pro-apoptosis protein Bax levels. Wound healing and cell migration were also decreased by treatment with GBE. Furthermore, we verified the effects of GBE on mitogenic signaling by investigating AKT target gene expression levels and revealed downregulated Sod2 and Bcl6 expression. We also confirmed that expression of inflammation-related genes decreased in a time-dependent manner. These results indicate that GBE has an anti-cancer effect on human gastric cancer cell lines. Further research on the mechanism of the anti-cancer effect will serve as basic data for possible anti-cancer drug development.

• Biomolecules & Therapeutics
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• 제20권6호
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• pp.513-519
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• 2012

Although the immense efforts have been made for cancer prevention, early diagnosis, and treatment, cancer morbidity and mortality has not been decreased during last forty years. Especially, lung cancer is top-ranked in cancer-associated human death. Therefore, effective strategy is strongly required for the management of lung cancer. In the present study, we found that novel daphnane diterpenoids, yuanhualine (YL), yuanhuahine (YH) and yuanhuagine (YG) isolated from the flower of Daphne genkwa (Thymelaeaceae), exhibited potent anti-proliferative activities against human lung A549 cells with the $IC_{50}$ values of 7.0, 15.2 and 24.7 nM, respectively. Flow cytometric analysis revealed that the daphnane diterpenoids induced cell-cycle arrest in the G0/G1 as well as G2/M phase in A549 cells. The cell-cycle arrests were well correlated with the expression of checkpoint proteins including the up-regulation of cyclin-dependent kinase inhibitor p21 and p53 and down-regulation of cyclin A, cyclin B1, cyclin E, cyclin dependent kinase 4, cdc2, phosphorylation of Rb and cMyc expression. In the analysis of signal transduction molecules, the daphnane diterpenoids suppressed the activation of Akt, STAT3 and Src in human lung cancer cells. The daphnane diterpenoids also exerted the potent anti-proliferative activity against anticancer-drug resistant cancer cells including gemcitabine-resistant A549, gefitinib-, erlotinib-resistant H292 cells. Synergistic effects in the growth inhibition were also observed when yuanhualine was combined with gemcitabine, gefitinib or erlotinib in A549 cells. Taken together, these findings suggest that the novel daphnane diterpenoids might provide lead candidates for the development of therapeutic agents for human lung cancers.