• 동의생리병리학회지
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• 제21권6호
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• pp.1555-1563
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• 2007

To idenifty effect of Bojungbangam-tang kakambang on Cisplatin-Induced G2/M Phase Arrest in Human Renal Proximal Tubular HK-2 Cells. Cytotoxicity of cisplatin was detected in HK-2 cells and the value of IC50 is about $25\;{\mu}M$. The treatment of cisplatin to HK-2 showed the G2/M phase cell cycle arrest. The ethanol extract of Bojungbangam-tang kakambang (EBTKB), a new herbal prescription composed of ten crude herbs, inhibited cisplatin-induced G2/M phase arrest in HK-2 cells. EBTKB increased G0/G1 peak in cisplatin-treated HK-2 cells. p53, p21 and p27 expression were increased in cisplatin-treated HK-2 cells. Inhibitory effect of EBTKB on cisplatin-induced G2/M phase arrest was accomplished through inhibition of p53, p21 and p27 expression. Also, reduced CDK2 and cyclin A expression by cisplatin were increased by EBTKB, but cyclin E was not changed. Reduction of ERK activation and increment of p38 activation by cisplatin were increased ERK activation and decreased p38 activation by EBTKB. Cisplatin had no effect on JNK activation, but EBTKB increased JNK activation. These results can suggest that EBTKB inhibits cisplatin-induced G2/M phase arrest in HK-2 cell through reduction of p53-dependent p21 and p27 protein, ERK activation and p38 inactivation.

• Nutrition Research and Practice
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• 제2권4호
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• pp.322-325
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• 2008

The aim of present study was to investigate the effects of kaempferol on cellular proliferation and cell cycle arrest and explore the mechanism for these effects in human breast carcinoma MDA-MB-453 cells. Cells were treated with kaempferol at various concentrations (ranging from 1 to $200\;{\mu}M$) for 24 and 48 hrs. Kaempferol significantly inhibited cancer cell growth in cells exposed to 50 and $10\;{\mu}M$ of kaempferol and incubated for 24 and 48 hrs, respectively. Exposure to kaempferol resulted in cell cycle arrest at the G2/M phase. Of the G2/M-phase related proteins, kaempferol down-regulated CDK1 and cyclin A and B in cells exposed to kaempferol. In addition, small DNA fragments at the sub-G0 phase were increased by up to 23.12 and 31.90% at 10 and $50\;{\mu}M$ incubated for 24 and 48 hrs, respectively. The kaempferol-induced apoptosis was associated with the up-regulation of p53. In addition, the phosphorylation of p53 at the Ser-15 residue was observed with kaempferol. Kaempferol inhibits cell proliferation by disrupting the cell cycle, which is strongly associated with the induction of arrest at G2/M phase and may induce apoptosis via p53 phosphorylation in human breast carcinoma MDA-MB-453 cells.

• Fisheries and Aquatic Sciences
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• 제24권1호
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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.

• 동의생리병리학회지
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• 제21권1호
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• pp.204-208
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• 2007

Chaga mushroom extract is well known as immune modulator and anti-cancer agent. However, the molecular mechanism by which Chaga exerts cell cycle arrest and apoptosis of cancer cells is poorly understood. In this study, we demonstrated anti-proliferative effects of Chaga extract on murine melanoma B16 cells. Chaga extract dose-dependently inhibited cell growth along with the arrest of G0/G1 phase and the induction of apoptotic cell death. Treatment with Chaga extract resulted in a decrease of cyclin E, cyclin D1, cdk 2, cdk 4 expression levels. Furthermore, in vivo inoculation study of B16 melanoma cells into Balb/c mice Chaga extract markedly suppressed the metastatic growth of tumor cells (6 folds, p<0.05,). These results indicate that Chaga mushroom extract induces apoptosis of B16 melanoma cells through arrest of G0/G1 phase in cell cycle.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6417-6421
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• 2015

Viscum album var (VAV) also known as mistletoe, has long been categorized as a traditional herbal medicine in Asia. In addition to its immunomodulating activities, mistletoe has also been used in the treatment of chronic hepatic disorders in China and Korea. There are numerous reports showing that VAV possesses anti-cancer effects, however influence on human hepatocarcinoma has never been elucidated. In the present study, hot water extracts of VAV was evaluated for its potential anti-cancer effect in vitro. SK-Hep1 cells were treated with VAV (50-400ug/ml) for both 24 and 48 hours then cell viability was measured by cell counting kit-8 (CCK-8). Flow cytometry analysis was used to measure the proportion of SK-Hep1 in the different stages of cell cycle. RT-PCR and Western blot analysis were conducted to measure expression of cell cycle arrest related genes and proteins respectively. VAV dose dependently inhibited the proliferation of SK-Hep1 cells without any cytotoxicity with normal Chang liver cell (CCL-13). Flow cytometry analysis showed that VAV extract inhibited the cell cycle of SK-Hep1 cells via G1 phase arrest. RT-PCR and Western blot analysis both revealed that cyclin dependent kinase 2 (Cdk2) and cyclin D1 gene expression were significantly down regulated while p21 was upregulated dose dependently by VAV treatment. Combined down regulation of Cdk2, Cyclin D1 and up regulation of p21 can result in cell death. These results indicate that VAV showed evidence of anti-cancer activity through G1 phase cell cycle arrest in SK-Hep1 cells.

• KSBB Journal
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• 제30권4호
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• pp.175-181
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• 2015

Cells proliferate via repeating process that growth and division. This process is G1, S, G2 and M four phases consists. Monitoring the progression of the cell cycle is a specific step that to be a continuous process is repeated to adjust the start of the next step. At this time, this process is called a Checkpoint. Currently, there are three known checkpoints that G1-S phase, G2-M phase, and the M phase. In this study, we confirmed that cell cycle arrest effects by ethanol extracts of Artemisia annua Linne (AAE) in Hep3B liver cancer cells. AAE was regulated proteins which involved in cell cycle such as pAkt, pMDM2, p53, p21, pCDK2 (T14/Y15). AAE induced cell cycle arrest in G1 checkpoint through phosphorylation of CDK2. Akt and p53 upstream is inhibited by AAE and p53 activated by non-activated pMDM2, p53 inhibitor. Thereby, activated p53 is transcript to p21 and activated p21 protein is combined with Cyclin E-pCDK2 complex. Therefore, we confirmed that AAE-induced cell cycle arrest was occurred by p21-Cyclin E-pCDK2 complex by inhibition of pAkt signal. Because of this cell cycle can't pass to S phase from G1 phase.

• 생명과학회지
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• 제26권9호
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• pp.1015-1021
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• 2016

Pyrimidine 유도체의 일종인 5-fluorouracil (5-FU)은 광범위하게 사용되는 항암제의 일종으로, thymidylate synthase의 활성을 억제시켜 핵산의 합성 및 대사기능 자애 유발 물질이다. 본 연구에서는 Ewing′s 육종 CHP-100 세포에서 5-FU의 증식억제와 연관된 기전 해석으로 시도하였다. 본 연구의 결과에 의하면, 5-FU 처리 시간의 경과에 따른 CHP-100 세포의 증식억제가 세포주기 G1 arrest 유발에 따른 것임을 알 수 있었다. 5-FU에 의한 CHP-100 세포의 G1 arrest는 retinoblastoma protein (pRB)의 탈인산화에 따른 전사인자 E2F-1 및 E2F-4와의 결합 촉진과 연관성이 있었다. 비록 5-FU 처리가 cyclin-dependent kinases의 발현에는 크게 영향을 주지 않았으나, 정상배지에서 배양된 대조군에 비하여 cyclin A 및 B의 발현이 5-FU 처리 시간 의존적으로 억제되었다. 또한 5-FU에 의한 CHP-100 세포의 G1 arrest는 apoptosis 유도와 연관이 있음을 핵 내 염색질의 응축에 따른 apoptotic body의 형성증가, poly (ADP-ribose) polymerase의 단편화 및 annexin V 염색 등을 통하여 확인하였다. 아울러 5-FU는 pro-apoptotic Bax 단백질의 발현 증가 및 anti-apoptotic Bcl-2의 발현 감소를 통한 mitochondrial membrane potential의 소실을 촉진시켰으며, 이로 인하여 미토콘드리아에서 세포질로의 cytochrome c 유리가 증가시켰음을 알 수 있었다. 따라서 본 연구의 결과는 5-FU에 의한 CHP-100 세포의 증식억제와 연관된 G1 arrest 및 apoptosis 유도에는 pRB의 인산화 억제 및 미토콘드리아 기능의 손상이 최소한 관여하고 있음을 의미하는 것이다.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1423-1428
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• 2014

Iso-suillin, a natural product isolated from Suillus luteus, has been shown to inhibit the growth of some cancer cell lines. However, the molecular mechanisms of action of this compound are poorly understood. The purpose of this study was to investigate how iso-suillin inhibits proliferation and induces apoptosis in a human hepatoma cell line (SMMC-7721). We demonstrated the effects of iso-suillin on cell proliferation and apoptosis in SMMC-7721 cells, with no apparent toxicity in normal human lymphocytes, using colony formation assays and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Western blotting was used to examine the expression of $G_1$ phase-regulated and apoptosis-associated protein levels in iso-suillin treated SMMC-7721 cells. The results indicated that iso-suillin significantly decreased viability, induced $G_1$ phase arrest and triggered apoptosis in SMMC-7721cells. Taken together, these results suggest the potential of iso-suillin as a candidate for liver cancer treatment.