• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6513-6519
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• 2015

Background: Recent attention on chemotherapeutic intervention against cancer has been focused on discovering and developing phytochemicals as anticancer agents with improved efficacy, low drug resistance and toxicity, low cost and limited adverse side effects. In this study, we investigated the effects of Curcuma C20-dialdehyde on growth, apoptosis and cell cycle arrest in colon and cervical cancer cell lines. Materials and Methods: Antiproliferative, apoptosis induction, and cell cycle arrest activities of Curcuma C20-dialdehyde were determined by WST cell proliferation assay, flow cytometric Alexa fluor 488-annexin V/propidium iodide (PI) staining and PI staining, respectively. Results: Curcuma C20 dialdehyde suppressed the proliferation of HCT116, HT29 and HeLa cells, with IC50 values of $65.4{\pm}1.74{\mu}g/ml$, $58.4{\pm}5.20{\mu}g/ml$ and $72.0{\pm}0.03{\mu}g/ml$, respectively, with 72 h exposure. Flow cytometric analysis revealed that percentages of early apoptotic cells increased in a dose-dependent manner upon exposure to Curcuma C20-dialdehyde. Furthermore, exposure to lower concentrations of this compound significantly induced cell cycle arrest at G1 phase for both HCT116 and HT29 cells, while higher concentrations increased sub-G1 populations. However, the concentrations used in this study could not induce cell cycle arrest but rather induced apoptotic cell death in HeLa cells. Conclusions: Our findings suggest that the phytochemical Curcuma C20-dialdehyde may be a potential antineoplastic agent for colon and cervical cancer chemotherapy and/or chemoprevention. Further studies are needed to characterize the drug target or mode of action of the Curcuma C20-dialdehyde as an anticancer agent.

• 생명과학회지
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• 제19권1호
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• pp.1-8
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• 2009

본 연구에서는 monofunctional alkylating agent인 N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) 에 의한 인체 백혈병 U937 세포의 증식억제에 관한 기전 확인하였다. MNNG에 의한 U937 세포의 증식억제는 세포주기 G2/M arrest 및 apoptosis 유방과 연관이 있었으며, MNNG 는 G2/M기 조절에 관여하는 주요 cyclin 및 Cdk들의 발현 수준에는 큰 영향이 없었으나 cyclin B1 및 Cdk2-associated kinase의 활성을 매우 저하시켰다. MNNG 처리로 Cdk inhibit p2l(WAF1/CIP1)이 전사 및 번역 수준에서 발연이 증가되었으며, p21 promoter 의 활성도 증가되었다. p21 promoter deletion constructs을 이용한 연구에서 MNNG의 responsive element 부위는 전사 개시 부위 113-61 부근임을 확인하였다. 이 결과들은 MNNG에 의한 cyclin/Cdk 복합체의 kinase 활성 저하가 p53 비의존적인 p21의 활성 증가에 기인한 것임을 보여주는 것이며, 이는 MNNG의 암세포에서의 항암기전을 이해하는 귀중한 자료로서 제공될 것으로 기대된다.

• 약학회지
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• 제55권5호
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• pp.391-397
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• 2011

KML001 reduced the proliferation of HCT116 cells in a concentration- and time-dependent manner without change of cell viability. Beclin-1 expression was significantly attenuated by KML001 (P<0.05), but no significant changes were observed in KML001-treated cells. The number of cells in G1 phase was increased 48 hr after KML001 treatment. Furthermore, a dramatic reduction in the frequency of beating and the number of embryoid bodies of the cells was noted after treatment. Taken together, KML001 suppresses the proliferation of HCT116 cells, which might be due to G1 phase arrest.

• 한국식품위생안전성학회지
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• 제24권3호
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• pp.267-272
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• 2009

우리 몸에 필수적인 미량원소인 셀레늄은 항암활성이 있는 것으로 알려져 있고, 역학적, 생태학적 그리고 임상시험을 종합해보면, 셀레늄은 종양, 특히 전립선암, 폐암, 대장암에 대한 위험성을 낮출 수 있을 것으로 생각되어진다. 기전연구에 따르면 셀레늄은 DNA single strand breaks와 활성산소종을 유도함으로써 종양을 억제하는 예방효능이 있는 것으로 밝혀지고 있다. 하지만, 아직까지 전립선암세포주에서 methylseloenol 대사체 중에 하나인 MSeA와 세포주기억제와의 관계에 대해서는 명확하게 밝혀져 있지 않은 실정이다. 따라서, 이번 연구에서는 전립선암세포주에서 셀레늄의 세포주기에 관한 효능을 확인해 보고자 하였다. 결과를 종합해보면, MSeA는 전립선암세포주에서 G1/S기 세포주기를 억제하고 DNA 합성을 방해하는 것으로 나타났고, 이러한 현상은 cyclin의존성 키나아제를 길항하는 단백질 중에 하나인 p27단백질의 발현을 증가시킴으로써 일어남을 확인하였다. 따라서, MSeA에 의해 유발되는 세포주기 억제가 전립선암 세포의 성장억제에 기여하는 것으로 사료된다.

• Nuclear Engineering and Technology
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• 제38권3호
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• pp.285-292
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• 2006

Thermoresistant (TR) clones of radiation-induced fibrosarcoma (RIF) cells have been reported to show an adaptive response to 1cGy of low dose radiation, and HSP25 and inducible HSP70 are involved in this process. In this study, to further elucidate the mechanism by which HSP25 and inducible HSP70 regulate the adaptive response, HSP25 or inducible HSP70 overexpressed RIF cells were irradiated with 1cGy and the cell cycle was analyzed. HSP25 or inducible HSP70 overexpressed cells together with TR cells showed increased G1 phase after 1cGy irradiation, while RIF cells did not. $[^3H]-Thymidine$ and BrdU incorporation also indicated that both HSP25 and inducible HSP70 are involved in G1 arrest after 1cGy irradiation. Molecular analysis revealed upregulation of p27Cip/Kip protein in HSP25 and inducible HSP70 overexpressed cells, and cotransfection of p27Cip/Kip antisense abolished the induction of the adaptive response and 1cGy-mediated G1 arrest. The above results indicate that induction of an adaptive response by HSP25 and inducible HSP70 is mediated by upregulation of p27Cip/Kip protein, resulting in low dose radiation-induced G1 arrest.

• 동의생리병리학회지
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• 제25권2호
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• pp.189-194
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• 2011

Nardostachys chinensis (N. Chinensis) belonging to the family Valerianaceae have been used in traditional medicine to elicit stomachic and sedative effects. The present study investigated the effects of water extract of N. Chinensis in human lymphoma U937 cells. The proliferation of U937 cells was decreased by N. Chinensis. Anti-proliferative effect of N. Chinensis on U937 cells was associated with G0/G1 phase arrest, which was mediated by regulating the expression of p21 and p27 protein. In addition, the levels of CDK2, CDK4, CDK6, Cyclin D3, and Cyclin A were decreased, but Cyclin D1, Cyclin D2 and Cyclin E were essentially undetectable. N. Chinensis induced the differentiation of U937 as shown by increased expression of differentiation surface antigen CD11b, but not CD14. Taken together, these results demonstrated that N. Chinensis potently inhibits the proliferation of U937 cells via the G0/G1 phase cell cycle arrest in association with p21 and p27, and induces granulocytic differentiation.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.138-138
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• 2002

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2006년도 춘계학술대회
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• pp.3-12
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• 2006

1 The present work was performed to investigate the effects of ginsenoside Rh2 on proliferation, cell cycle-regulation and differentiation of human leukemia HL-60 cells as well as the underlying mechanisms for these effects. 2 Ginsenoside Rh2 potently inhibited the proliferation of HL-60 cells in both a dose- and time-dependent manner with an $IC_{50}$, $20{\mu}M$. 3 DNA flow-cytometry indicated that ginsenoside Rh2 markedly induced a $G_1$ phase arrest of HL-60 cells. 4 Among the $G_1$ phase cell cycle-related proteins, the levels of cyclin-dependent kinase(CDK)4, 6 and cyclin D1, cyclin D2, cyclin D3 were reduced by ginsenoside Rh2, whereas the steadystate levels of CDK2 and cyclin E were unaffected. 5 The protein levels of a CDK inhibitor p16, $p21^{CIP1/WAF1}$ and $p27^{KIP1}$ were markedly increased by ginsenoside Rh2. 6 Ginsenoside Rh2 markedly enhanced the binding of $p21^{CIP1/WAF1}$ and $p27^{KIP1}$ with CDK2 and CDK6, resulting in the reduced activity of both kinases and the hypophosphorylation of Rb protein. 7 We furthermore suggest that ginsenoside Rh2 is a potent inducer of the differentiation of HL-60 cells, based on observations such as a reduction of the nitroblue tetrazolium level, an increase in the esterase activities and phagocytic activity, morphology changes, and the expression of CD11b, CD14, CD64 and CD66b surface antigens. 8 In conclusion, the onset of ginsenoside Rh2-induced the $G_0/G_1$ arrest of HL-60 cells prior to the differentiation is linked to a sharp up-regulation of the $p21^{CIP1/WAF1}$ level and a decrease in the CDK2, CDK4 and CDK6 activities. This is the first report demonstrating that ginsenoside Rh2 potently inhibits the proliferation of human promyelocytic HL-60 cells via the $G_1$ phase cell cycle arrest and differentiation induction.

• 동의생리병리학회지
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• 제24권1호
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• pp.55-60
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• 2010

Caesalpinia sappan L. (C. sappan) has long been used in traditional medicine as an emmenagogue, hemostatic and anti-inflammatory agent. The present study investigated the effects of water extract of C. sappan in human lymphoma U937 cells. The proliferation of U937 cells was decreased by C. sappan in a dose-dependently manner. Anti-proliferative effect of C. sappan on U937 cells was associated with G2/M phase arrest, which was mediated by regulating the expression of p21 protein. Moreover, phosphorylation of JNK and p38 was increased by C. sappan. Blockade of JNK and p38 was significantly inhibited C. sappan-induced G2/M phase arrest. Taken together, these results suggest that Anti-proliferative effect of C. sappan on U937 is assocated with G2/M phase cell cycle arrest by expression of p21 protein and, JNK and p38 activation.

• Natural Product Sciences
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• 제18권1호
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• pp.16-21
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• 2012

Honokiol, a naturally occurring neolignan mainly found in Magnolia species, has been shown to have the anti-angiogenic, anti-invasive and cancer chemopreventive activities, but the molecular mechanism of actions has not been fully elucidated yet. In the present study, we investigated the effect of honokiol on the growth inhibitory activity in cultured SNU-638 human gastric cancer cells. We found that honokiol exerted potent antiproliferative activity against SNU-638 cells. Honokiol also arrested the cell cycle progression at the G0/G1 phase and induced the apoptotic cell death in a concentration-dependent manner. The cell cycle arrest was well correlated with the downregulation of Rb, cyclin D1, cyclin A, cyclin E, and CDK4 expression, and the induction of cyclin-dependent kinase inhibitor p27. The increase of sub-G1 peak by honokiol was closely related to the induction of apoptosis, which was evidenced by the induction of DNA fragmentation, the cleavage of poly(ADPribose) polymerase, and the sequential activation of caspase cascade. These findings suggest the cell cycle arrest and induction of apoptosis might be one possible mechanism of actions for the anti-proliferative activity of honokiol in human gastric cancer cell.