• 한국환경성돌연변이발암원학회지
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• 제26권3호
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• pp.69-76
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• 2006

2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin(TCDD) is a ubiquitous, persistent environmental contaminant and the most powerful carcinogen categorized by IARC. Although the mechanism of carcinogenesis by TCDD is poorly understood, several studies have shown that the skin is one of target organs far TCDD. In this study, we investigated the neoplastic transformation of human keratinocyte-derived cell line, HaCaT, by chemical transformation method using N-methyl-N'-nitro-N-nitrorsoguanidine(MNNG) and TCDD. We found that subsequent exposure to TCDD for 3 weeks after initial exposure to MNNG markedly induced transformed cells. It was suggested that TCDD can act as a potent promoter in HaCaT cells. Furthermore, these transformed cells showed morphological alternations in soft agar and increased telomerase activity. Therefore, the TCDD treatment of HaCaT cells by initiated with MNNG could promote neoplastic transformation without stimulation by exogenous growth factors. As a result, TCDD had a strong potency as a promoter in nontumorigenic immortalized human epidermal keratinocytes.

• 동의생리병리학회지
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• 제18권2호
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• pp.500-506
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• 2004

The objective of the present study was to investigate the effects of aqueous extract from the healthful decoction utilizing Phellinus linteus (HDPL) on the growth of human lung carcinoma A549 cells. HDPL treatment declined the cell viability of A549 cells in a concentration-dependent manner and the anti-proliferative effects by HDPL treatment were associated with morphological changes such as membrane shrinking and cell rounding up. HDPL treatment did not affect the distribution of the cell cycle. Western blot analysis and RT-PCT data revealed that the levels of tumor suppressor p53 and cyclin-dependent kinase inhibitor p21WAF1/CIP1 in HDPL-treated A549 cells were remained unchanged. However, HDPL treatment inhibited the expression of cyclooxygenase-2 (COX-2) mRNA and protein in a concentration-dependent fashion. Additionally, the expression of human telomerase reverse transcriptase (hTERT), a main determinant of the telomerase enzymatic activity, was progressively down-regulated by HDPL treatment. Taken together, these findings suggest that HDPL-induced inhibition of human lung cancer cell proliferation is associated with the inhibition of several major growth regulatory gene products, such as COX-2 and hTERT, and HDPL may have therapeutic potential in human lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6549-6556
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• 2013

Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression and relapse, and thus represent a critical target for therapeutic intervention. Hence, it is extremely urgent to explore new therapeutic strategies directly targeting LSCs for acute myelogenous leukemia (AML) therapy. We show here that Angelica sinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), effectively inhibited human AML $CD34^+CD38^-$ cell proliferation in vitro culture in a dose-dependent manner while sparing normal hematopoietic stem and progenitor cells at physiologically achievable concentrations. Furthermore, ASP exerted cytotoxic effects on AML K562 cells, especially LSC-enriched $CD34^+CD38^-$ cells. Colony formation assays further showed that ASP significantly suppressed the formation of colonies derived from AML $CD34^+CD38^-$ cells but not those from normal $CD34^+CD38^-$ cells. Examination of the underlying mechanisms revealed that ASP induced $CD34^+CD38^-$ cell senescence, which was strongly associated with a series of characteristic events, including up-regulation of p53, p16, p21, and Rb genes and changes of related cell cycle regulation proteins P16, P21, cyclin E and CDK4, telomere end attrition as well as repression of telomerase activity. On the basis of these findings, we propose that ASP represents a potentially important agent for leukemia stem cell-targeted therapy.

• 동의생리병리학회지
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• 제21권6호
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• pp.1437-1449
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• 2007

In this study, the effect of extract of Corydalis yanhusuo (ECT) used in Oriental medicine therapy was investigated on the cell growth and apoptosis of HepG2 human hepatoma cells. It was found that ECT could inhibit the cell growth effectively in a dose-dependent manner, which was associated with morphological change and apoptotic cell death such as formation of apoptotic bodies, DNA fragmentation and increased populations of apoptotic-sub G1 phase. And we observed the effects of ECT on loss of mitochondrial membrane potential (MMP), using the JC-1 probe by DNA flow cytometric analysis. Apoptosis of HepG2 cells by ECT was associated with a down-regulation of anti apoptotic Bcl-2 expression, inhibitor of apoptosis proteins (IAPs) expression and proteolytic activation of caspase-3 and caspase-9. However, ECT did not affect the pro-apoptotic Bax expression and activity of caspase-8. ECT treatment also concomitant degradation and /or inhibition of poly (ADP-ribose) polymerase (PARP), phospholipase C-1 ($PLC{\gamma}1$). Furthermore, ECT treatment caused a dose-dependent inhibition of iNOS and cyclooxygenase-2 (Cox-2). Additionally ECT have been implicated in the regulation of telomerase expression. ECT treatment induced the down-regulation of telomerase reverse transcriptase mRNA (hTERT) expression of HepG2 cells. Taken together, these findings suggest that ECT may be a potential chemotherapeutic agent for the control of HepG2 human hepatoma cells.

• Reproductive and Developmental Biology
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• 제36권4호
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• pp.275-281
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• 2012

Embryonic stem cell-preconditioned microenvironment is important for cancer cells properitities by change cell morphology and proliferation. This microenvironment induces cancer cell reprogramming and results in a change in cancer cell properties such as differentiation and migration. The cancer microenvironment affects cancer cell proliferation and growth. However, the mechanism has not been clarified yet. Using the ES-preconditioned 3-D microenvironment model, we provide evidence showing that the ES microenvironment inhibits proliferation and reduces oncogenic gene expression. But ES microenvironment has no effect on telomerase activity, cell viability, cellular senescence, and methylation on Oct4 promoter region. Furthermore, methylation of Nanog was increase on ES-preconditioned microenvironment and supports results that no difference on RNA expression levels. Taken together, these results demonstrated that in the ES-preconditioned 3-D microenvironment is a crucial role for cancer cell proliferation not senescence.

• 생명과학회지
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• 제26권11호
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• pp.1320-1329
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• 2016

본 연구는 다당체의 한 종류인 penta-O-galloyl-${\beta}$-D-glucose (PGG)가 사람의 여러 조직에서 기원하는 여러 암세포주(A-549, MDA-MB-231, U87-MG, MCF-7 및 PANC-1), 정상 MRC-5 태아 섬유아세포 그리고 사랑니에서 유래한 간엽줄기세포(DPSCs)에 미치는 세포독성 효과를 조사하였다. $IC_{50}$값은 다른 세포주에 비해 높은 증식률을 나타내는 A-549 및 MDA-MB-231 암세포주에서 유의적으로 낮게 관찰되었다. 10 uM의 PGG가 포함된 배양액에서 세포를 7일 동안 배양한 결과, 세포배가시간은 모든 세포주에서 유의적으로 늘어났고, 세포배가시간과 $IC_{50}$값의 관계를 조사한 결과, 세포배가시간이 늘어남에 따라 $IC_{50}$값은 비례적으로 증가됨을 증명하였다. 또한, 10 uM의 PGG로 처리된 세포주들은 노화와 관련된 ${\beta}-galactosidase$의 활성도가 높게 관찰되었다. 특히, telomerase 활성도는 A-549 및 MDA-MB-231 암세포주에서 다른 세포주에 비하여 현저히 감소하는 것을 관찰하였다. 이러한 결과를 바탕으로 PGG는 높은 증식률을 보이는 암세포주에서 높은 세포독성효과를 나타내어 잠재적인 항암물질임을 증명하였다.

• 생명과학회지
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• 제31권3호
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• pp.266-279
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• 2021

본 연구에서는 다양한 사람의 암세포주(A-549, MCF-7, MDA-MB-231, U87-MG, AGS, MKN-74 및 SNU-601 세포)와 정상세포주(MRC-5 섬유아세포 및 사랑니 유래 중간엽성 줄기세포에 토복령 추출물(Smilax china L. extract, SCLE)을 처리하여 세포 사멸 효과를 조사하였다. SCLE 처리 후, MTT 분석에서 여러 암세포주는 정상세포주보다 유의적으로 휠씬 낮은 반억제농도값을 나타내었고, 세포는 세포부착력의 소실로 인한 세포사멸(anoikis)이 관찰되었다. 또한, SCLE를 처리한 A-549, AGS 및 MCF-7 암세포주에서 세포의 생존성과 말단소립 복원효소의 활성도를 조사하였을 때, SCLE 처리 후 4일째에 세포의 생존성과 말단소립 복원효소의 활성도가 현저히 줄어드는 것을 관찰하였다. 또한, SCLE를 처리한 A-549, AGS 및 MCF-7 암세포주에서 세포 주기의 G1기에서 세포 성장이 정지되었고,세포 사멸이 유의적으로 증가하는 것을 알 수 있었다. 그러나, SCLE 처리는 rho 단백질의 활성과 관련 없는 세포부착력의 소실과 세포 사멸이 유도되는 것을 관찰하였다. 이 연구의 결과를 바탕으로 토복령 추출물은 정상 세포보다는 암세포에 특이적으로 세포부착력의 소실과 세포 사멸을 유도하여, 이 추출물에 포함된 물질을 이용한 항암 연구에 응용될 수 있을 것으로 판단된다.

• BMB Reports
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• 제44권8호
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• pp.512-516
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• 2011

Establishment of immortalized human dermal papilla cells (DPCs) retaining the characteristics of DPCs would be a great help for hair researchers. We recently established a simian virus 40T (SV40T)-transformed human DP cell line (SV40TDPC). However, the cell line senesced around passage 25 and ceased proliferation. In this study, we introduced the human telomerase reverse transcriptase (hTERT) gene into SV40T-DPC and established an immortalized human DP cell line. The cell line, SV40T-hTERT-DPC, did not induce tumors when inoculated into nude mice. SV40T-hTERT-DPC maintained morphology of early passage DPCs, expressed markers of DPCs, and retained responses to Wnt/${\beta}$-catenin and bone morphogenic protein (BMP) signaling pathways known to be required for hair-inducing activity of DPCs. The data strongly suggest that SV40T-hTERT-DPC retains many characteristics of human DPCs in vivo without malignant transformation.

• 대한세포병리학회지
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• 제17권1호
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• pp.18-26
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• 2006

Transitional cell carcinoma of the urinary bladder is common in the genitourinary tract. The gold standard for the diagnosis of bladder cancer has been cystoscopy, along with urine cytology. Cystoscopy is an invasive and relatively expensive technique. By comparison, urine cytology is easy to perform and specific for a diagnosis of bladder cancer, although less sensitive, especially in low-grade tumors. For this reason, there has been a need for superior noninvasive technology to increase our confidence in being able to detect bladder cancer. There are many reports of the various urinary tests that are available to facilitate the diagnosis. In this article, I reviewed the literature on urinary markers and tests that may be clinically useful, including fluorescence in situ hybridization, uCyt+/Immunocyte, the $BTA^{(R)}$ test, the NMP 22TM, the $FDP^{(R)}$ test, the telomerase activity test, the HA and HAse tests, and flow cytometry. Most of these tests have a higher sensitivity and specificity than cytology. However, urine cytology has the highest specificity, especially in individuals with a high-grade tumor. We conclude that no urinary markers or tests can replace the role of cystoscopy along with cytology in the diagnosis of transitional cell carcinoma of the bladder. However, some markers could be used adjunctively to increase the diagnostic accuracy during screening or during the postoperative follow-up examination of patients with bladder cancer.

• Journal of Microbiology and Biotechnology
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• 제22권3호
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• pp.431-435
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• 2012

In this study, we describe a novel approach to achieve replicative selectivity of conditionally replicative adenovirus that is based upon trans-splicing ribozyme-mediated replacement of cancer-specific RNAs. We developed a specific ribozyme that can reprogram human telomerase reverse transcriptase (hTERT) RNA to induce adenoviral E1A gene expression selectively in cancer cells that express the RNA. Western blot analysis showed that the ribozyme highly selectively triggered E1A expression in hTERT-expressing cancer cells. RT-PCR and sequencing analysis indicated that the ribozyme-mediated E1A induction was caused via a high fidelity trans-splicing reaction with the targeted residue in the hTERT-expressing cells. Moreover, reporter activity under the control of an E1A-dependent E3 promoter was highly transactivated in hTERT-expressing cancer cells. Therefore, adenovirus containing the hTERT RNA-targeting trans-splicing ribozyme would be a promising anticancer agent through selective replication in cancer cells and thus specific destruction of the infected cells.