• Title/Summary/Keyword: cancer cell suppression.

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Suppression of CDK2 expression by siRNA induces cell cycle arrest and cell proliferation inhibition in human cancer cells

  • Long, Xiang-E.;Gong, Zhao-Hui;Pan, Lin;Zhong, Zhi-Wei;Le, Yan-Ping;Liu, Qiong;Guo, Jun-Ming;Zhong, Jiu-Chang
    • BMB Reports
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    • v.43 no.4
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    • pp.291-296
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    • 2010
  • Cyclin-dependent kinase 2 (CDK2) is a member of serine/threonine protein kinases, which initiates the principal transitions of the eukaryotic cell cycle and is a promising target for cancer therapy. The present study was designed to inhibit cdk2 gene expression to induce cell cycle arrest and cell proliferation suppression. Here, we constructed a series of RNA interference (RNAi) plasmids which can successfully express small interference RNA (siRNA) in the transfected human cells. The results showed that the RNAi plasmids containing the coding sequences for siRNAs down-regulated the cdk2 gene expression in human cancer cells at the mRNA and the protein levels. Furthermore, we found that the cell cycle was arrested at G0G1 phases and the cell proliferation was inhibited by different siRNAs. These results demonstrate that suppression of CDK2 activity by RNAi may be an effective strategy for gene therapy in human cancers.

Zinc finger and BTB domain-containing protein 3 is essential for the growth of cancer cells

  • Lim, Ji-Hong
    • BMB Reports
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    • v.47 no.7
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    • pp.405-410
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    • 2014
  • ZBTB3 belongs to the Zinc finger and BTB/POZ domain containing transcription factor family; however, its biological role has rarely been studied. We demonstrate for the first time, to our knowledge, that ZBTB3 is an essential factor for cancer cell growth via the regulation of the ROS detoxification pathway. Suppression of ZBTB3 using two different short hairpin RNAs in human melanoma, lung carcinoma, and breast carcinoma results in diminished cell growth. In addition, we found that suppression of ZBTB3 activates a caspase cascade, including caspase-9, -3, and PARP leading to cellular apoptosis, resulting from failed ROS detoxification. We identified that ZBTB3 plays an important role in the gene expression of ROS detoxification enzymes. Our results reveal that ZBTB3 may play a critical role in cancer cell growth via the ROS detoxification system. Therefore, therapeutic strategies that target ZBTB3 could be used in selective cancer treatments.

Acetylshikonin Inhibits Human Pancreatic PANC-1 Cancer Cell Proliferation by Suppressing the NF-κB Activity

  • Cho, Seok-Cheol;Choi, Bu Young
    • Biomolecules & Therapeutics
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    • v.23 no.5
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    • pp.428-433
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    • 2015
  • Acetylshikonin, a natural naphthoquinone derivative compound, has been used for treatment of inflammation and cancer. In the present study, we have investigated whether acetylshikonin could regulate the NF-${\kappa}B$ signaling pathway, thereby leading to suppression of tumorigenesis. We observed that acetylshikonin significantly reduced proliferation of several cancer cell lines, including human pancreatic PANC-1 cancer cells. In addition, acetylshikonin inhibited phorbol 12-myristate 13-acetate (PMA) or tumor necrosis-${\alpha}$ (TNF-${\alpha}$)-induced NF-${\kappa}B$ reporter activity. Proteome cytokine array and real-time RT-PCR results illustrated that acetylshikonin inhibition of PMA-induced production of cytokines was mediated at the transcriptional level and it was associated with suppression of NF-${\kappa}B$ activity and matrix metalloprotenases. Finally, we observed that an exposure of acetylshikonin significantly inhibited the anchorage-independent growth of PANC-1 cells. Together, our results indicate that acetylshikonin could serve as a promising therapeutic agent for future treatment of pancreatic cancer.

Effect of Growth Inhibition in Hep3B cell and HeLa cell by treatment of Euonymus alatus(Thunb.) Sieb extracts (귀전우(鬼箭羽)(Euonymus alatus(Thunb.) Sieb)가 간암세포(肝癌細胞)(Hep3B)와 자궁암세포(子宮癌細胞)(HeLa)의 성장억제(成長抑制)에 미치는 영향(影響)에 관한 연구(硏究))

  • Choi, Dal-Yeong
    • The Journal of Dong Guk Oriental Medicine
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    • v.7 no.2
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    • pp.155-162
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    • 1999
  • Euonymus alatus(Thunb.) Sieb has been used for cancer theraphy such as Liver cancer, esophagus cancer, stomach cancer, and uterine cancer in folk. Eupolyphaga simemsis(ES) extracted from Euonymus alatus(Thunb.) Sieb increases HDL-C/TC ratio and LCAT activity. TGF-${\beta}$ and Insulin has been Knoen as factors to induce the supression of proliferation of Hep3B, Human hepatoblastoma cell. Plasma HDL3-C involved in carbohydrate methabolism in the liver was maintained in low level by Euonymus alatus(Thunb.) Sieb. The low level of plasma HDL3-C suppresses the transition from normal liver to Fat liver. Finally, this resuly in suppression of cancer in liver. In this study, Euonymus alatus(Thunb.) Sieb showed higher cell toxicity in hepatoblastoma cell(Hep3B) compared to the uterine cancer cell(HeLa). This means Euonymus alatus(Thunb.) Sieb seems not to affect in the all kinds of cancer. In future, we will study whether Euonymus alatus(Thunb.) Sleb have an effect on the liver cancer induced by virus and hepatocellular carcinoma. Also, the mechanims of suppression of cell proliferation in HCC need to investigated.

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Cell Cycle and Cancer

  • Park, Moon-Taek;Lee, Su-Jae
    • BMB Reports
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    • v.36 no.1
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    • pp.60-65
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    • 2003
  • Cancer is frequently considered to be a disease of the cell cycle. As such, it is not surprising that the deregulation of the cell cycle is one of the most frequent alterations during tumor development. Cell cycle progression is a highly-ordered and tightly-regulated process that involves multiple checkpoints that assess extracellular growth signals, cell size, and DNA integrity. Cyclin-dependent kinases (CDKs) and their cyclin partners are positive regulators of accelerators that induce cell cycle progression; whereas, cyclin-dependent kinase inhibitors (CKIs) that act as brakes to stop cell cycle progression in response to regulatory signals are important negative regulators. Cancer originates from the abnormal expression of activation of positive regulators and functional suppression of negative regulators. Therefore, understanding the molecular mechanisms of the deregulation of cell cycle progression in cancer can provide important insights into how normal cells become tumorigenic, as well as how cancer treatment strategies can be designed.

Brazilin Inhibits of TPA-induced MMP-9 Expression Via the Suppression of NF-${\kappa}B$ Activation in MCF-7 Human Breast Carcinoma Cells

  • Kim, Byeong-Soo
    • Journal of Food Hygiene and Safety
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    • v.25 no.3
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    • pp.209-214
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    • 2010
  • Metastasis is the primary cause of from breast cancer mortality. Cell migration and invasion play important roles in neoplastic metastasis. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix (ECM), plays an important role in cancer cell invasion. NF-${\kappa}B$ is transcription factor important in the regulation of MMP-9, as the promoter of MMP-9 gene contains binding sites for NF-${\kappa}B$. Brazilin, an active component of sappan wood (Caesalpinia sappan), decreases TPA-induced MMP-9 expression and invasion in MCF-7 cells. Also, brazilin suppressed NF-${\kappa}B$ activation in TPA-treated MCF-7 cells. Taken together, we demonstrated that the inhibition of TPA-induced MMP-9 expression and cell invasion by brazilin is mediated by the suppression of the NF-${\kappa}B$ pathway in MCF-7 cells. This result suggest brazilin provide a potential therapeutic app roach for the treatment of breast cancer.

TrkB Promotes Breast Cancer Metastasis via Suppression of Runx3 and Keap1 Expression

  • Kim, Min Soo;Lee, Won Sung;Jin, Wook
    • Molecules and Cells
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    • v.39 no.3
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    • pp.258-265
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    • 2016
  • In metastatic breast cancer, the acquisition of malignant traits has been associated with the increased rate of cell growth and division, mobility, resistance to chemotherapy, and invasiveness. While screening for the key regulators of cancer metastasis, we observed that neurotrophin receptor TrkB is frequently overexpressed in breast cancer patients and breast cancer cell lines. Additionally, we demonstrate that TrkB expression and clinical breast tumor pathological phenotypes show significant correlation. Moreover, TrkB expression was significantly upregulated in basal-like, claudin-low, and metaplastic breast cancers from a published microarray database and in patients with triple-negative breast cancer, which is associated with a higher risk of invasive recurrence. Interestingly, we identified a new TrkB-regulated functional network that is important for the tumorigenicity and metastasis of breast cancer. We demonstrated that TrkB plays a key role in regulation of the tumor suppressors Runx3 and Keap1. A markedly increased expression of Runx3 and Keap1 was observed upon knockdown of TrkB, treatment with a TrkB inhibitor, and in TrkB kinase dead mutants. Additionally, the inhibition of PI3K/AKT activation significantly induced Runx3 and Keap1 expression. Furthermore, we showed that TrkB enhances metastatic potential and induces proliferation. These observations suggest that TrkB plays a key role in tumorigenicity and metastasis of breast cancer cells through suppression of Runx3 or Keap1 and that it is a promising target for future intervention strategies for preventing tumor metastasis and cancer chemoprevention.

Proliferative and Inhibitory Activity of Siberian ginseng (Eleutherococcus senticosus) Extract on Cancer Cell Lines; A-549, XWLC-05, HCT-116, CNE and Beas-2b

  • Cichello, Simon Angelo;Yao, Qian;Dowell, Ashley;Leury, Brian;He, Xiao-Qiong
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4781-4786
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    • 2015
  • Siberian ginseng (Eleutherococcus senticosus) is used primarily as an adaptogen herb and also for its immune stimulant properties in Western herbal medicine. Another closely related species used in East Asian medicine systems i.e. Kampo, TCM (Manchuria, Korea, Japan and Ainu of Hokkaido) and also called Siberian ginseng (Acanthopanax senticosus) also displays immune-stimulant and anti-cancer properties. These may affect tumour growth and also provide an anti-fatigue effect for cancer patients, in particular for those suffering from lung cancer. There is some evidence that a carbohydrate in Siberian ginseng may possess not only immune stimulatory but also anti-tumour effects and also display other various anti-cancer properties. Our study aimed to determine the inhibitory and also proliferative effects of a methanol plant extract of Siberan ginseng (E. senticosus) on various cancer and normal cell lines including: A-549 (small cell lung cancer), XWLC-05 (Yunnan lung cancer cell line), CNE (human nasopharyngeal carcinoma cell line), HCT-116 (human colon cancer) and Beas-2b (human lung epithelial). These cell lines were treated with an extract from E. senticosus that was evaporated and reconstituted in DMSO. Treatment of A-549 (small cell lung cancer) cells with E. senticosus methanolic extract showed a concentration-dependent inhibitory trend from $12.5-50{\mu}g/mL$, and then a plateau, whereas at 12.5 and $25{\mu}g/mL$, there is a slight growth suppression in QBC-939 cells, but then a steady suppression from 50, 100 and $200{\mu}g/mL$. Further, in XWLC-05 (Yunnan lung cancer cell line), E. senticosus methanolic extract displayed an inhibitory effect which plateaued with increasing dosage. Next, in CNE (human nasopharyngeal carcinoma cell line) there was a dose dependent proliferative response, whereas in Beas-2 (human lung epithelial cell line), an inhibitory effect. Finally in colon cancer cell line (HCT-116) we observed an initially weak inhibitory effect and then plateau.

Effects of Duchesnea Indica of Colorectal Adenocarcinoma Cells (사매가 대장암 세포에 미치는 영향)

  • Lee, Do-Hyoung;Kim, Jin-Sung;Yoon, Sang-Hyub;Ryu, Ki-Won;Ryu, Bong-Ha
    • The Journal of Internal Korean Medicine
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    • v.26 no.2
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    • pp.310-319
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    • 2005
  • Objectives: The aim is to identify any anti-tumor effects of Duchesnea indica(Andr.) Focke on colon cancer cells. Materials & Methods: Colo201 human adenocarcinoma cells were obtained from American Type Culture Collection. The boiled extract of Duchesnea indica(Andr.) Focke was added (10 and 20 microliters) to cultures and observed at 0, 6, and 12 hours, and at 12-hour intervals thereafter. Morphological changes in colon cancer cells were observed through an inverted microscope, Destruction of colon cancer cells was measured through Trypan blue exclusion testing. Suppression of the viability of colon cancer cells were measured via MTT assay. Anti-cancer mechanisms in the cell cycle of colon cancer cells were analysed via flow cytometry. Results: After introduction of Duchesnea indica(Andr.) Focke to cultures several changes were seen. Significant atrophy of the nucleus and cytoplasm of colon cancer cells was observed, indicating cell injury. Destruction of colon cancer cells was observed in direct proportion to dosage and duration. Suppression of viability of colon cancer cells for each test group was greater than that of the control group increasingly over time(36h, 48h, 60h, 72h), which was statistical significant (p<0.05). Cell numbers of the mitosis phase of the colon cancer cell cycle reduced. Conclusions: Statistcally significant anti-tumor effects of Duchesnea indica(Andr.) Focke were observed in this in vitro experiment. Results support a role for Duchesnea indica(Andr.) Focke in treatment of colon cancer. though it will required progressive research to develop a practical treatment.

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Effects of Duchesnea indica on Human Stomach Cancer Cells(KATOIII) (사매의 KATOIII 위암세포(胃癌細胞)에 대(對)한 항암효능(抗癌效能))

  • Lim, Joong-Hwa;Kim, Jin-Sung;Yoon, Sang-Hyub;Ryu, Ki-Won;Ryu, Bong-Ha
    • The Journal of Internal Korean Medicine
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    • v.26 no.2
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    • pp.302-309
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    • 2005
  • Background : Death by cancer, malignant tumor, is on the increase around the world. In South Korea, cancer is the number one cause of death, and, in South Korea, stomach cancer is the most common form of cancer. This may be due to genetic and enviornmental factors. Because stomach cancer is so prevalent here, this study was undertaken. Objectives: This study was conducted to investigate the anti-cancer effects of Duchesnea indica(Andr.) Focke. in human stomach cancer cells(KATOIII). Materials & Methods: For human stomach cancer cells KATO III cells were obtained from Korea Cell Line Bank. The water decoction of Duchesnea indica(Andr.) Focke was added to cultures. First, morphological changes were examined under an inverted microscope. The destruction of stomach cancer cells was measured through Trypan blue exclusion testing, and suppression of viability of stomach cancer cells was measured via MTT assay. Anti-cancer mechanisms were assessed by analyzing the cell cycle. Results & Conclusions : In morphologic change, stomach cancer cells showed the withdrawn and floating appearance that is typical in cellular impairment. In each test group more stomach cancer cells were killed than in the control group to a statistically significant degree. Each test group showed more suppression of viability of stomach cancer cells than that of the control group to a statistically significant degree. Analysis of the cell cycle showed that Duchesnea indica(Andr.) Focke inhibited division of stomach cancer cells. This experiment yielded empirical evidence for Duchesnea indica(Andr.) Focke as a statistically significant anticarcinogen, specifically against stomach cancer.

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