• Title/Summary/Keyword: cancer cell growth inhibition

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Inhibition of Cell Proliferation and Migration by miR-509-3p That Targets CDK2, Rac1, and PIK3C2A

  • Yoon, Sena;Han, Eunji;Choi, Young-Chul;Kee, Honghwan;Jeong, Yongsu;Yoon, Jaeseung;Baek, Kwanghee
    • Molecules and Cells
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    • v.37 no.4
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    • pp.314-321
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    • 2014
  • CDK2 is a key regulator of cell cycle progression. In this study, we screened for miRNAs targeting CDK2 using a luciferase-3'-untranslated region reporter assay. Among 11 hit miRNAs, miR-509-3p reduced CDK2 protein levels and significantly inhibited cancer cell growth. Microarray, Western blotting, and luciferase reporter analyses revealed additional targets of miR-509-3p, including Rac1 and PIK3C2A. Overexpression of miR-509-3p induced G1 cell-cycle arrest and inhibited colony formation and migration. RNAi experiments indicated that the growth-inhibitory effects of miR-509-3p may occur through down-regulation of CDK2, Rac1, and PIK3C2A. Targeting of multiple growth regulatory genes by miR-509-3p may contribute to effective anti-cancer therapy.

A Study on the Growth Inhibition of Human Colon Cancer Cells by Eucommial Lea Extract (두충의 인체 암세포 증식억제 효과 연구)

  • 황우익
    • The Korean Journal of Food And Nutrition
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    • v.5 no.1
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    • pp.13-22
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    • 1992
  • This study was divised to observe the inhibitory effect of growth rate of human colon cancer cells by Eucommial leaf extract, in vitro. Three species of human colon cancer cells, HRT-18, HCT-48 and HT-29, were used for the experiment. Each extract of Eucommial leaf was prepared by extraction with water, 95% alcohol, acetone, chloroform and petroleum ether, and then the inhibitory effect of each extract on the growth rate of cells was compared with control group and each other. The experimental results obtained are summarized as follows; 1. Inhibitory effects on growth rate of human colon cancer fells were strongest in the petroleum ether extract and next in the chloroform extract. 2. Inhibitory effects on the growth rate of the cancer cells by extracts of water, 95% alcohol and acetone were weaker than that of petroleum ether and chloroform. 3. Inhibitory effect of each extract on the cancer cell growth was shown most strong activity in HT-29, and was in order of HRT 18 and HCT-48. In view of the results, it could be suggested that inhibitory effects of non-polar solvent's extracts against the cancer cell growth were more stronger than that of polar solvents and the effects were indicated difference according to the species of the cells.

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The Study of Anti-cancer Mechanism with Bee Venom and Melittin on Human Prostatic Cancer Cell (전립선 암세포에 대한 봉약침액(蜂藥浸液) 및 Melittin 약침액(藥浸液)의 항암(抗癌) 기전(機轉) 연구(硏究))

  • Kim, Kyung-Tae;Song, Ho-Sueb
    • Journal of Acupuncture Research
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    • v.22 no.6
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    • pp.37-50
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    • 2005
  • Objectives : The purpose of this study was to investigate the anti-caner effect of Bee Venom and Melittin on the prostatic cancer cell(PC-3). The goal of study is to ascertain whether Bee Venom and Melittin inhibits the cell growth and cell cycle of PC-3, or the expression of relative genes and whether the regression of PC-3 cell growth is due to cell death or the expression of gene related to apoptosis. Methods : After the treatment of Pc-3 cells with Bee Venom and Melittin, we performed Fluorescence microscope, MTT assay, Western blotting, Flow cytometry, PAGE electrophoresis and Surface plasmon resonance analysis to identify the cell viability, apoptosis and gene related to apoptosis. Results : 1. Compared with Control cell, the inhibition of cell growth reduced in proportion with the dose of Bee Venom or Melittin($0{\sim}10{\mu}g/ml$) in PC-3. 2. In PC-3, Cell viabilities of Bee Venom or Melittin treatment was decreased significantly. 3. The nucli of Control cells were stained round and homogenous in DAPI staining, but those of PC-3 were stained condense and splitted. 4. In PC-3, apoptosis of Bee Venom or Melittin treatment was increased significantly. 5. Bax, Caspase-3 and P ARP of Bee Venom or Melittin treatment was increased significantly and Bcl-2 of Bee Venom or Melittin treatment was decreased significantly. Caspase-9 of Bee venom treatment was increased significantly. Conclusion : These results indicate that Bee Venom and Melittin inhibits the growth of prostate cancer cells, has anti-cancer effects by inducing apoptosis. We wish that the anti-cancer effects of Bee Venom and Melittin are used to clinical caner treatment.

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INDUCTION OF APOPTOSIS IN ORAL CANCER CELL LINE THROUGH AN RECOMBINANT HCCS-1 ADENOVIRUS (재조합 HCCS-1 아데노바이러스를 이용한 구강암 세포주의 세포사멸 유발)

  • Kim, Chang-Hyen;Lee, Dong-Ju;Lee, ll-Kyu;Kim, Myung-Jin;Kim, Jin-Woo;Pyo, Sung-Woon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.31 no.4
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    • pp.306-311
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    • 2005
  • Despite advances in surgery, radiotherapy, and chemotherapy, the survival of patients with oral squamous cell carcinoma has not significantly improved over the past several decades. Gene therapy is currently under investigation and shows us new possibility of cancer curing method. This experiment was undergone to find out the cell growth inhibition effect and evidence of apoptosis by HCCS-1(human cervical cancer suppressor-1), one of the candidates of tumor suppressor gene, transducted to human oral cancer cell line. To determine the efficiency of the adenovirus as a gene delivery vector cell line was transducted with LacZ gene and analysed with X-gal staining. Northern blot was performed to confirm the transfection with HSCC-1 gene and cell viability was assessed by cell cytotoxicity assay using cell count kit(CCK). To show the evidence of apoptosis, DNA fragmentation assay and flow cytometry(FACS) were performed. We had successfully construct the recombinant HSCC-1 adenovirus(Ad5CMV-HCCS-1), and importation efficiency was 20% at 2 MOI(multiplicity of infection), 80% at 20 MOI. Northern blot analysis showed that a single 0.6kb mRNA transcript was expressed in Ad5CMV-HCCS-1 transducted cell lines. As a result of CCK, when comparing to control subjects, transducted group showed 50% growth inhibition. In DNA fragmentation assay, according to increasing of MOI, DNA volume was diminished. In FACS analysis, DNA distribution showed fragmentation. This results imply that HCCS-1gene has growth inhibition effect in human oral cancer cell lines through apoptosis induction.

Study on the Anti-tumor Effects of Extracts from Lepista nuda Mushroom (민자주방망이버섯 추출물의 항암 효과에 대한 연구)

  • Lee, Yang-Suk;Han, Joo-Young;Joo, Eun-Yong;Shin, Seung-Ryeul;Kim, Nam-Woo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.3
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    • pp.317-322
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    • 2005
  • This study was carried to investigate the inhibition effects of Lepista nuda mushroom extracts on the growth of the human cancer (HepG2, KATOⅢ, AGS) cells. The fraction Ⅰ of Lepista nuda mushroom extracts strongly inhibited to 71.4-91.8% for the growth of cancer cells. The growth of cancer HepG2, KATOⅢ and AGS cell which treated with 0.5 and 1㎎/mL of hot water fraction I was inhibited to 71.4% and 85.5%, 45.0% and 86.6%, 71.6% and 90.7% respectively. The growth of cancer cell HepG2, KATOⅢ and AGS which treated with 0.5 and 1㎎/mL of microwave fraction I was inhibited to 79.8% and 85.2%, 78.6% and 88.9%, 85.8% and 91.8%, respectively. The inhibition ratios of cancer cell growth were higher by microwave extracts than hot water extracts. And the more fraction were insoluble for water, the more inhibition ratios of cancer cell growth were lower.

Induction of Apoptosis by Samgibopae-tang in Human Non-small-cell Lung Cancer Cells (인체폐암세포 NCI-H460 및 A549의 증식에 미치는 삼기보폐탕의 영향 비교)

  • Heo, Man-Kyu;Park, Cheol;Choi, Young-Hyun;Kam, Cheol-Woo;Park, Dong-Il
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.4
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    • pp.973-981
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    • 2007
  • In the present study, we investigated the antiproliferative activity of the water extract of Samgibopae-tang (SGBPT) in NCI-H460 and A549 non-small-cell lung cancer cell lines. We found that exposure of A549 cells to SGBPT resulted in the growth inhibition in a dose-dependent manner as measured by MTT assay, however SGBPT did not affect the growth of NCI-H460 cells. The antiproliferative effect by SGBPT treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. SGBPT treatment did not induce the cell cycle arrest in both cell lines, however the frequency of sub-G1 population was concentration-dependently increased by SGBPT treatment in A549 cells. SGBPT treatment partially induced the expression of tumor suppressor p53 in A549 cells and the expression of cyclin-dependent kinase inhibitor p21(WAF1/CIP1) was markedly increased in both transcriptional and translational levels in A549 cells. The up-regulation of p21 by SGBPT occurred in a similar a concentration dependent manner to that observed with the inhibition of cell viability and induction of sub-G1 population of the cell cycle. However SGBPT treatment did not affect other growth regulation-related genes such as early growth response-1 (Egr-1), nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), inducible nitric oxide synthease (iNOS), cyclooxygenases (COXs), telomere-regulatory factors in A549 as well as NCI-H460 cells. Taken together, these findings suggested that SGBPT-induced inhibition of human lung carcinoma A549 cell growth was aoosciated with the induction of p21 and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of SGBPT.

Alternative drug therapies are superior to epidermal growth factor receptor -targeted chemotherapeutic drug responses in non-small cell lung cancer

  • Sikdar, Sourav;Khuda-Bukhsh, Anisur Rahman
    • CELLMED
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    • v.3 no.2
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    • pp.10.1-10.8
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    • 2013
  • Cancer is one of the major dreaded diseases causing high mortality. Lung cancer is second in position of all cancer related deaths and mainly divided into two morphologic sub-types: small-cell lung cancer and non-small cell lung cancer (NSCLC). NSCLC is an aggressive neoplasm which hardly responds to any conventional chemotherapy. Epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinase that is mainly over-expressed in NSCLC. EGFR is mainly involved in the pathogenesis and progression of different carcinoma. In vivo and in vitro studies suggest that EGFR and EGF like peptides are often over-expressed in human NSCLC and these proteins are able to induce cell transformation. The conventional therapies mostly inhibit the EGFR activity and expression level in human NSCLC with the use of some EGFR-inhibitors like HKI-272, EKB569, CL-387785 etc. and some synthetic chemotherapeutic drugs like erlotinib, gefitinib, plumbagin, docetaxel, cisplatin etc., alone or in combination of two or more drugs. These therapies selectively act by competitive inhibition of the binding of adenosine triphosphate to the tyrosine kinase domain of the EGFR, resulting in inhibition of the EGFR signaling pathway. But these chemotherapeutic drugs have some cytotoxic activities to the normal cells and have some adverse side-effects. Recent studies on some traditional alternative therapies including some herbal and plant extracts, active ingredients like curcumin, different homeopathic drugs, etc. can target EGFR-signalling in NSCLC with less toxic side-effects are being currently developed.

Induction of cell cycle arrest and apoptosis by an indirubin analog, a CDK inhibitor, in human lung cancer cells

  • Lee, Jong-Won;Moon, Myung-Ju;Kim, Yong-Chul;Lee, Sang-Kook
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.91.2-91.2
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    • 2003
  • Cyclin-dependent kinases (CDKs) regulate the cell division cycle, apoptosis, transcription and differentiation. Inhibition of CDK is a promising target in development of anti-cancer agents. An indirubin analog (AGM01l), a CDK inhibitor, is a synthetic compound that inhibits human cancer cell growth in vitro. AGM01l showed a potent cytotoxicity in cultured human cancer cell lines (IC$\sub$50/ = 5.43 ${\mu}$M for A549, human colon cancer cell; IC$\sub$50/ = 1.21 ${\mu}$M for SNU-638, human stomach cancer cell; IC$\sub$50/ 9.23 ${\mu}$M for HL-60, human leukemia cell). (omitted)

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Induction of Apoptosis by Samgibopae-tang in Human Non-small-cell Lung Cancer Cells (인체폐암세포 NCI-H460 및 A549의 apoptosis 유발에 미치는 삼기보배탕의 영향)

  • Heo, Man-Kyu;Heo, Tae-Yool;Kim, Ki-Tak;Byun, Mi-Kwon;Kim, Jin-Young;Sim, Sung-Heum;Kim, Koang-Lock;Kam, Cheol-Woo;Park, Dong-Il
    • The Journal of Internal Korean Medicine
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    • v.28 no.3
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    • pp.473-491
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    • 2007
  • Objectives : This study was designed to investigate the antiproliferative activity of the water extract of Samgibopae-tang (SGBPT) in NCI-H460 and A549 non-small-cell lung cancer cell lines Methods : In this study, we measured the subsistence, form of NCI-H460 and A549 non-small-cell lung cancer cell by hemocytometer and DAPI staining. In each cell, we analyzed DNA fragmentation. reverse transcription-polymerase chain reaction and measured activity of caspase-3, caspase-8 and caspase-9. Results and Conclusions : We found that exposure of A549 cells to SGBPT resulted in growth inhibition in a dose-dependent manner. butSGBPT did not affect the growth of NCI-H460 cells. The antiproliferative effect by SGBPT treatment in A549 cells was associated with morphological changes. SGBPT treatment partially induced the expression of DR5 cells and the expression of Faswas markedly increased in both transcriptional and translational levels in A549 cells. SGBPT treatment partially induced the expression of Bcl-2, Bcl-XL and the expression of Bid was markedly decreased in translational levels in A549 cells. However, SGBPT treatment did not affect the expression of IAP family in A549 orNCI-H460 cells. SGBPT treatment partially induced the expression of caspase-3, caspase-8, caspase-9 activity which markedly increased in a dose-dependent manners in A549 cells. The fragmental development of PARP and ${\beta}$-catenin protein was observed in A549 cells by SGBPT treatment. SGBPT treatment induced the expression of PLC-${\gamma}1$ protein which decreased in A549 cells. SGBPT treatment partially induced the expression of DFF45/ICAD which markedly increased in a dose-dependent manner in A549 cells. Taken together. these findings suggested that SGBPT-induced inhibition of human lung carcinoma did not affect NCI-H460 cell growth. However, SGBPT-induced inhibition of human lung carcinoma A549 cell growth was associated with the induction of death receptor and mitochondrial pathway. The results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of SGBPT.

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Anticancer activity of subfractions containing pure compounds of Chaga mushroom (Inonotus obliquus) extract in human cancer cells and in Balbc/c mice bearing Sarcoma-180 cells

  • Chung, Mi-Ja;Chung, Cha-Kwon;Jeong, Yoon-Hwa;Ham, Seung-Shi
    • Nutrition Research and Practice
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    • v.4 no.3
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    • pp.177-182
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    • 2010
  • The Chaga mushroom (Inonotus obliquus) has been used in folk medicine to treat cancers. However, limited information exists on the underlying anticancer effects of the major component of I. obliquus in vivo. We hypothesize that the pure compounds ($3{\beta}$-hydroxy-lanosta-8,24-dien-21-al, inotodiol and lanosterol, respectively) separated from I. obliquus would inhibit tumor growth in Balbc/c mice bearing Sarcoma-180 cells (S-180) in vivo and growth of human carcinoma cells in vitro. To test this hypothesis, the growth inhibition of each subfraction isolated from I. obliquus on human carcinoma cell lines (lung carcinoma A-549 cells, stomach adenocarcinoma AGS cells, breast adenocarcinoma MCF-7 cells, and cervical adenocarcinoma HeLa cells) was tested in vitro. Then, after S-180 implantation, the mice were fed a normal chow supplemented with 0, 0.1 or 0.2 mg of subfraction 1, 2 or 3 per mouse per day. All of the subfractions isolated from I. obliquus showed significant cytotoxic activity against the selected cancer cell lines in vitro. Subfraction 1 was more active than subfraction 2 and subfraction 3 against the A549, AGS and MCF-7 cancer cell lines in vitro. In in vivo results, subfraction 1 isolated from I. obliquus at concentrations of 0.1 and 0.2 mg/mouse per day significantly decreased tumor volume by 23.96% and 33.71%, respectively, as compared with the control. Subfractions 2 and 3 also significantly inhibited tumor growth in mice bearing S-180 as compared with the control mouse tumor. Subfraction 1 isolated from I. obliquus showed greater inhibition of tumor growth than subfractions 2 and 3, which agrees well with the in vitro results. The results suggest that I. obliquus and its compounds in these subfractions isolated from I. obliquus could be used as natural anticancer ingredients in the food and/or pharmaceutical industry.