• Journal of Life Science
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• v.29 no.6
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• pp.679-687
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• 2019

Litsea populifolia, a plant species of the Lauraceae family, is widely distributed in the tropical and subtropical areas of Asia. The phylogenetic relationships and botanical characteristics of L. populifolia have been reported; however, its anti-oxidative and anti-cancer activities remain unclear. In this study, we evaluated the anti-oxidative and anti-cancer effects of ethanol extracts of L. populifolia (EELP) together with the molecular mechanism of its anti-cancer activity in human lung adenocarcinoma A549 cells. EELP showed significant anti-oxidative effects with a 50% inhibitory concentration at $11.71{\mu}g/ml$, which was measured by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. EELP exhibited cytotoxic activity and induced cell cycle arrest at the G1 phase in A549 cells in a dose-dependent manner, whereas EELP did not have the cytotoxic effect on the normal human lung cell line IMR90. Treatment with EELP also resulted in a decreased expression of G1/S transition-related molecules-including cyclin-dependent kinase (CDK) 2, CDK6, cyclin D1, and cyclin E-both for the transcription and translation levels. EELP-induced G1 arrest was associated with the phosphorylation of checkpoint kinase 2 (CHK2), p53, cell division cycle 25 homolog A (CDC25A), and the reduction of CDC25A expression in A549 cells. Collectively, these results suggest that EELP may exert an anti-cancer effect by cell cycle arrest at the G1 phase through both p53-dependent and p53-independent (ATM/CHK2/CDC25A/CDK2) pathways in A549 cells.

• BMB Reports
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• v.43 no.4
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• pp.273-278
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• 2010

The cell cycle is regulated by cyclin-dependent kinase (CDK)-cyclin complexes as well as other regulators. We isolated Kip-related protein 4 (KRP4) cDNA that encodes 289 amino acids including six conserved domains. To investigate the expression pattern of KRP4 as well as of other cell cycle-related genes associated with plant hormones, Arabidopsis seedlings were cultured on MS medium containing auxin or cytokinin. All seedlings treated with phytohormones displayed an increased proportion of cells in S phase. A higher proportion of cells in G2 phase was observed in seedlings treated with NAA. RT-PCR confirmed that the expression of KRP4 was decreased after treatment with phytohormones, and that CDKA and D-type cyclin transcription was increased. Additionally, mitotic cyclins were up-regulated by NAA treatment. These results suggest that KRP4 as well as other cell cycle-related genes might contribute to the control of plant growth in response to exogenous hormones.

• Fisheries and Aquatic Sciences
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• v.24 no.1
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• pp.1-9
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• 2021

Human prostate cancer is the second most frequently diagnosed cancer worldwide, and its incidence rate continues to increase. Advanced prostate cancer is more difficult to treat than early forms due to its chemotherapy resistance. There is need for more effective agents that can inhibit the progression of advanced prostate cancer. Demethoxyfumitremorgin C (DMFTC) was isolated from the fermentation extract of the marine fungus Aspergillus fumigatus. Antiproliferative activity of DMFTC against human prostate cancer PC3 cells was examined through cell cycle analysis by flow cytometry, the fluorescent nuclear imaging analysis with propidium iodide (PI), and proteins expression related to cell cycle arrest and apoptosis were investigated via Western blotting. DMFTC inhibited PC3 cells growth through G1 phase cell cycle arrest and apoptosis induction. It activated the tumor suppressor p53 and the Cdk inhibitor p21, which regulate the cell progression into the G1 phase. Additionally, PI-positive late apoptotic non-viable cells were increased and the expression levels of the G1-positive downstream regulators cyclin D, cyclin E, Cdk2, and Cdk4 were decreased by DMFTC treatment. These results suggest that DMFTC induces G1 arrest and apoptosis induction through regulation of p53/p21-dependent cyclin-Cdk complexes, and it may be a useful therapeutic agent for the treatment of human advanced prostate cancer.

• Journal of Life Science
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• v.19 no.7
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• pp.871-877
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• 2009

We investigated the effects of sodium butyrate, a histone deacetylase inhibitor, on the cell cycle progression in human monocytic leukemia U937 cells. Exposure of U937 cells to sodium butyrate resulted in growth inhibition, G1 arrest of the cell cycle and induction of apoptosis in a dose-dependent manner as measured by MTT assay and flow cytometry analysis. The increase in G1 arrest was associated with the down-regulation in cyclin D1, E, A, cyclin-dependent kinase (Cdk) 4 and 6 expression, and up-regulation of Cdk inhibitors such as p21 and p27. Sodium butyrate treatment also inhibited the phosphorylation of retinoblastoma protein (pRB) and p130, however, the levels of transcription factors E2F-1 and E2F-4 were not markedly modulated. Furthermore, the down-regulation of phosphorylation of pRB and p130 by this compound was associated with enhanced binding of pRB and E2F-1, as well as p130 and E2F-4, respectively. Overall, the present results demonstrate a combined mechanism involving the inhibition of pRBjp130 phosphorylation and induction of Cdk inhibitors as targets for sodium butyrate that may explain some of its anti-cancer effects in U937 cells.

• Journal of Periodontal and Implant Science
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• v.33 no.3
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• pp.415-437
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• 2003

Ginseng Radix(GR) had been used widely from oriental medicine and the effects of it have been investigated by many researchers. The purpose of present study was to investigate the effects of GR on the cell cycle progression and its molecular mechanism in human fetal osteoblast. The results were as follows. Increased cell proliferation was observed in cells exposed to 100 ng/ml, 10 ng/ml of GR-1 at 12 hours and 24 hours, 1 ${\mu}g$/ml of GR-1 at 48 hours, and 100 ${\mu}g$/ml, 10 ${\mu}g$/ml of GK-2 at 12 hours, all treatment groups of GR-2 at 24 hours(p<0.05). S phase and G1 phase was increased in the group of treated with 100 ng/ml of GR-1, with 10 ${\mu}g$/ml and 1 ${\mu}g$/ml of GR-2, with 100 ${\mu}g$/ ml and 10 ${\mu}g$/ml of GR-3 in the cell cycle analysis. The cell cycle regulation protein levels of Cyclin D1, Cyclin E, CDK 2. CDK 4 and CDK 6 were increased in the group of treated with 1 ${\mu}g$/ml and 100 ng/ml of GR-1, with 10 ${\mu}g$/ml and 1 ${\mu}g$/ml of GR-2, with 100 ${\mu}g$/ ml and 10 ${\mu}g$/ml of GR-3. On the other hand, p21 was decreased in the treatment group with 1 ${\mu}g$/ml and 100 ng/ml of GR-1, with 10 ${\mu}g$/ml and 1 ${\mu}g$/ml of GR-2, 10 ${\mu}g$/ml of GR-3, and p53 and p16 was decreased in the treatment group with 100 ng/ml of GR-1, 100 ${\mu}g$/ml and GR-3 and pRb was decreased in the all treatment groups except 1 ${\mu}g$/ml of GR-1. These results suggested that GR increases the cell proliferation and the cell cycle progression in human fetal osteoblast, which is linked to increased cell cycle regulation protein levels of Cyclin D1 , Cyclin E, CDK 2, CDK 4, CDK 6 and decreased cell cycle regulation protein levels of p21, pRb.

• The Journal of Korean Medicine
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• v.36 no.4
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• pp.19-34
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• 2015

Objectives: This study was performed to investigate the anti-tumor effect of O. japonicus extracts on intrahepatic cholangiocarcinoma cell line SNU-1079. Methods: Cholangiocarcinoma SNU-1079 cells were treated with various concentrations of O. japonicus DW and EtOH extracts ($0-300{\mu}g/ml$) for 24, 48 or 72 h. Cell viability was evaluated through a PMS/MTS assay, and the apoptosis rate was examined through ELISA assay and flow cytometry analysis. The mRNA expression of apoptosis- and cell cycle progression-related genes (Bcl-2, Mcl-1, Bax, Survivin, Cyclin D1, and p21) was evaluated using real-time PCR, and the caspase activity was examined using immunoblot analysis. Results: O. japonicus extracts inhibited cell proliferation and increased apoptosis rate in both ELISA assay and flow cytometry analysis. O. japonicus extracts decreased Bcl-2, Mcl-1, Survivin, and Cyclin D1 mRNA expression and increased Bax mRNA level. O. japonicus extracts also increased Caspase-3 activation. Overall, O. japonicus DW extracts were more effective than EtOH extracts. Conclusions: O. japonicus inhibited cell proliferation and induced apoptosis in SNU-1079 cells via mitochondria -mediated intrinsic pathway, which leads to Caspase-3 activation. The results indicate that O. japonicus is a potential therapeutic herb with anti-tumor effect against intrahepatic cholangiocarcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3041-3044
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• 2013

Background: The non-steroidal anti-inflammatory drug (NSAID) aspirin (acetylsalicylic acid) is an inhibitor of cyclooxygenase enzymes. Recent studies have shown that aspirin could be used as an anti-tumor drug. Triptolide, the major compound extracted from the Chinese herb Tripteryglum wilfordii Hook.f, has now been shown that it can inhibit tumor growth. The aim of this study was to analyze the anti-tumor efficiency of aspirin and triptolide in cervical cancer cells. Methods: Viability of cervical cancer cell lines was assessed by the MTT method at various concentrations of aspirin and triptolide. Siha and HeLa cell apoptotic analysis was performed by flow cytometry. Real time-PCR and Western Blotting were used to analyze the expression of Bcl-2/Bax, Cyclin D1 and p16. Results: Viability in the combination group was significantly decreased as compared with either drug used alone. Expression change of Bcl-2/Bax, CyclinD1 and p16 appeared to play an important role in the synergistic killing effect on cervical cancer cell apoptosis. Conclusion: Aspirin and triptolide combination treatment may have synergistic anti-tumor effects on cervical cancer cells.

• Journal of Applied Biological Chemistry
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• v.65 no.4
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• pp.269-275
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• 2022

Betula platyphylla extract includes various materials which showed biological activity such as terpenoids. For this reason, Betula platyphylla extract has been used to alleviate inflammation. In this study, extract of Betula platyphylla was obtained and purified using several solvents and evaluated whether they showed effect on prevention of hair loss. Cell cytotoxicity assay was performed to investigate the effect of extracts on cell proliferation. Western blotting was performed to observe the changes in expression of several related growth factors such as β-catenin, VEGF, IGF1, and cyclin D. Also, 5-α-reductase activity was measured. The ethyl acetate extract was divided into four partial extracts and named as H3-1, H3-2, H3-3, and H3-4. The H3-2 extract showed proliferation activity of human derma papilla cell and increased the protein expression of several related growth factors such as β-catenin, VEGF, IGF1, and cyclin D, comparable to the effect of Ethyl 3,4,5-Trimethoxy Benzoate (ETB)and Lupeol (LPO). Moreover, we found that the fraction H3 was shown to decrease 5-α-reductase activity while ETB and LPO had no significant effect on 5-α-reductase activity.

• Journal of Periodontal and Implant Science
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• v.29 no.3
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• pp.593-607
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• 1999

치주인대세포는 치주인대의 유지와 개조에 있어서 중요한 역할을 담당하는 섬유아세포성 세포로서, 세포에 가해진 여러가지 조건에 따라 다양한 표현형의 변화를 나타내는 것으로 알려져 있다. 기계적 응력은 치주인대세포의 세포증 식과 밀접히 연관되어 있는 것으로 알려져 있으며, 이는 세포주기 조절인자들의 발현을 증가 시킴으로써 이루어질 것으로 생각되나 그 자세 한 작용기전은 알려져 있지 않다. 그러므로 이 연구의 목적은 기계적 응력이 사람 치주인대세 포의 세포증식과 세포주기 조절인자의 발현에 미치는 영향을 연구하기 위하여 사람 치주인대 세포에 기계적 응력을 가한 후 세포증식을 관찰하고 , 세포주기조절인자들인 p 53 , $p21^{WAF1/CIP1}$ cyclin-dependent kinases(cdks), cyclins 및 proliferating cell nuclear antigen(PCNA)의 단백질 발현 변화를 연구하였다. 본 연구에 사용한 사람 치주인 대세포는 교정치료를 목적으로 발거한 건전한 사람 소구치의 치주인대로부터 explantation culture하여 얻은 후 계대배양을 시행하여 제6 계대의 세포를 사용하였다. 배양한 사람 치주인 대세포를 55-mm Petriperm dish당 $1{\times}10^4$ 개를 분주하고, dish당 1kg의 기계적 응력을 가하면서 12일동안 세포배양을 시행하였다. 사람 치주인대세포의 세포증식은 기계적 응력을 가한 후 8-12일 사이에 현저히 증가하였으며, PCNA 단백질의 발현은 기계적 응력을 가한 후 6-10일 사이에 현저히 증가하였다. 또한 기계적 응력은 사람 치주 대세포의 cdk4, cdk6, cdk2 및 cyclin D1 단백질의 발현을 다소 증가 시켰으나, p53 및 $p21^{WAF1/CIP1}$ 단백질의 발현은 큰 변화가 없었다. 이상의 결과 서 기계적 응력은 사람 치주인대세포 의 p53 및 $p21^{WAF1/CIP1}$ 단백질 발현의 변화 없이 cdks 단백질 발현을 증가시킴으로써 세포증식을 증가시키는 것으로 생각된다.

• Journal of Periodontal and Implant Science
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• v.35 no.1
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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.