• Title/Summary/Keyword: anti-proliferative

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Anti-proliferative Effect of Tetra-arsenic Oxide (TetraAs®) in Human Gastric Cancer Cells in Vitro

  • Chung, Won-Heui;Koo, Hye-Jin;Kuh, Hyo-Jeong
    • Journal of Pharmaceutical Investigation
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    • v.37 no.5
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    • pp.305-309
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    • 2007
  • Arsenic compounds have been used to treat various diseases including cancer in oriental medicine. Arsenic trioxide ($As_2O_3,\;Trisenox^{(R)}$) has been used for the treatment of leukemia and its anti-solid tumor activity has also been reported recently. Tetra-arsenic oxide ($As_4O_6,\;TetraAs^{(R)}$) is a newly developed arsenic compound which has shown an anticancer activity in some human cancer cell lines. The purpose of this study was to evaluate the anti-gastric cancer potential of TetraAs and to search for an agent with synergistic interaction with TetraAs against human gastric cancers. We analysed anti-proliferative effect of TetraAs when given alone and in combination with other chemotherapeutic agents such as 5-FU, paclitaxel, and cisplatin in SNU-216, a human gastric cancer cell line. The $IC_{50}$ of these 4 anti-cancer drugs ranged from 5.8 nM to $7.5\;{\mu}M$ with a potency rank of order paclitaxel>TetraAs>cisplatin>5-FU. TetraAs showed 10-fold greater potency than 5-FU and cisplatin at the same effect level of $IC_{50}$. TetraAs+5-FU and TetraAs+paclitaxel showed synergistic and additive interaction, respectively. On the other hand, TetraAs with cisplatin group appeared to be strongly antagonistic. Apoptotic population was measured and compared between single and combination treatment. The apoptotic cells for the combination of TetraAs+5-FU showed significant increase compared to single TetraAs treatment. On the contrary, TetraAs+cisplatin showed less apoptotic cells compared to TetraAs or cisplatin alone treatment. Overall, our results indicate that TetraAs can be effectively combined with 5-FU or paclitaxel, but not with cisplatin for synergistic anti-cancer effect, which warrants further evaluation using in vivo models.

Anti-Proliferative and Pro-Apoptotic Activities of 4-Methyl-2,6-bis(1-phenylethyl)phenol in Cancer Cells

  • Sung, Nak Yoon;Kim, Seung Cheol;Kim, Yun Hwan;Kim, Gihyeon;Lee, Yunmi;Sung, Gi-Ho;Kim, Ji Hye;Yang, Woo Seok;Kim, Mi Seon;Baek, Kwang-Soo;Kim, Jong-Hoon;Cho, Jae Youl
    • Biomolecules & Therapeutics
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    • v.24 no.4
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    • pp.402-409
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    • 2016
  • It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells.

A Fermented Ginseng Extract, BST204, Inhibits Proliferation and Motility of Human Colon Cancer Cells

  • Park, Jong-Woo;Lee, Jae-Cheol;Ann, So-Ra;Seo, Dong-Wan;Choi, Wahn-Soo;Yoo, Young-Hyo;Park, Sun-Kyu;Choi, Jung-Young;Um, Sung-Hee;Ahn, Seong-Hoon;Han, Jeung-Whan
    • Biomolecules & Therapeutics
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    • v.19 no.2
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    • pp.211-217
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    • 2011
  • Panax ginseng CA Meyer, a herb from the Araliaceae, has traditionally been used as a medicinal plant in Asian countries. Ginseng extract fermented by ginsenoside-${\beta}$-glucosidase treatment is enriched in ginsenosides such as Rh2 and Rg3. Here we show that a fermented ginseng extract, BST204, has anti-proliferative and anti-invasive effects on HT-29 human colon cancer cells. Treatment of HT-29 cells with BST204 induced cell cycle arrest at $G_1$ phase without progression to apoptosis. This cell cycle arrest was accompanied by up-regulation of tumor suppressor proteins, p53 and p21$^{WAF1/Cip1}$, down-regulation of the cyclin-dependent kinase/cyclins, Cdk2, cyclin E, and cyclin D1 involved in $G_1$ or $G_1/S$ transition, and decrease in the phosphorylated form of retinoblastoma protein. In addition, BST204 suppressed the migration of HT-29 cells induced by 12-O-tetradecanoylphorbol-13-acetate, which correlated with the inhibition of metalloproteinase-9 activity and extracellular signal-regulated kinase activity. The effects of BST204 on the proliferation and the invasiveness of HT-29 cells were similar to those of Rh2. Taken together, the results suggest that fermentation of ginseng extract with ginsenoside-${\beta}$-glucosidase enhanced the anti-proliferative and the anti-invasive activity against human colon cancer cells and these anti-tumor effects of BST204 might be mediated in part by enriched Rh2.

Anti-Proliferative Activity of OD78 Is Mediated through Cell Cycle Progression by Upregulation p27kip1 in Rat Aortic Vascular Smooth Muscle Cells

  • Tudev, Munkhtsetseg;Lim, Yong;Park, Eun-Seok;Kim, Won-Sik;Lim, Il-Ho;Kwak, Jae-Hwan;Jung, Jae-Kyung;Hong, Jin-Tae;Yoo, Hwan-Soo;Lee, Mi-Yea;Pyo, Myoung-Yun;Yun, Yeo-Pyo
    • Biomolecules & Therapeutics
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    • v.19 no.2
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    • pp.187-194
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    • 2011
  • Atherosclerosis and post-angiography restenosis are associated with intimal thickening and concomitant vascular smooth muscle cell (VSMC) proliferation. Obovatol, a major biphenolic component isolated from the Magnolia obovata leaf, is known to have anti-inflammatory and anti-tumor activities. The goal of the present study was to enhance the inhibitory effects of obovatol to improve its potential as a preventive or therapeutic agent in atherosclerosis and restenosis. Platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic smooth muscle cells (RASMCs) was examined in the presence or absence of a newly synthesized obovatol derivative, OD78. The observed anti-proliferative effect of OD78 was further investigated by cell counting and [$^3H$]-thymidine incorporation assays. Treatment with 1-4 ${\mu}M$ OD78 dose-dependently inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated RASMCs. Accordingly, OD78 blocked PDGF-BB-induced progression from the $G_0/G_1$ to S phase of the cell cycle in synchronized cells. OD78 decreased the expression levels of CDK4, cyclin E, and cyclin D1 proteins, as well as the phosphorylation of retinoblastoma protein and proliferating cell nuclear antigen; however, it did not change the CDK2 expression level. In addition, OD78 inhibited downregulation of the cyclin-dependent kinase inhibitor (CKI) $p27^{kip1}$. However, OD78 did not affect the CKI $p21^{cip1}$ or phosphorylation of early PDGF signaling pathway. These results suggest that OD78 may inhibit PDGF-BB-induced RASMC proliferation by perturbing cell cycle progression, potentially through $p27^{kip1}$ pathway activation. Consequently, OD78 may be developed as a potential anti-proliferative agent for the treatment of atherosclerosis and angioplasty restenosis.

Anti-leukemic effects of JIPAESAN and its components on leukemic cells HL-60 (인간백혈병(人間白血病) 세포주(細胞株)에서 지패산(芷貝散)의 작용(作用)에 관(關)한 연구(硏究))

  • Hwang Kee-Myoung
    • Herbal Formula Science
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    • v.10 no.1
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    • pp.143-155
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    • 2002
  • In the hope of identifying anti-leukemic agents from traditional herbal medicines. this study was designed to investigate the anti-leukemic effects of the herbal medicine Jipaesan, which is composed of Angelica Dahurica and Fritillariae Verticillata. in acute promyeloid leukemia HL-60 cells. Jipaesan showed anti-proliferative effect through the induction of differentiation and apoptosis in HL -60 cells. Verticinone as a major differentiating agent and imperatorin as major apoptosis-inducing agent were isolated from the water extracts of F. Verticillata and A. Dahurica, respectively. Combined treatment of HL-60 cells with two major compounds showed synergy in the induction of differentiation. Since the induction of differentiation and/or apoptosis has therapeutic values in curing acute leukemic diseases. Jipaesan could be useful as an anti-leukemic agent.

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Heme Oxygenase Inducers from Natural Products

  • Chung, Hun-Taeg;Pae, Hyun-Ock;Park, Byung-Min;Oh, Gi-Su
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2004.04a
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    • pp.21-35
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    • 2004
  • Heme oxygenase (HO)-l catabolizes heme into three products: carbon monoxide, bilirubin, and free iron. HO-l serves as a protective gene by virtue of the anti-inflammatory, anti-apoptotic and anti-proliferative actions of one or more of these three products. HO-l can be regarded as a potential therapeutic target in a variety of oxidant-mediated and inflammatory diseases. In this respect, it would be valuable to develop potent and selective inducers of HO-1 for therapeutic use. Here, we have shown that 1,2,3,4,6-penta-O-galloyl-beta-D-glucose, catalposide and dehydrocostus lactone are potent inducers of HO-1 and exert cytoprotective and anti-inflammatory activities via HO-1-ependent machanism.

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Inhibitory Effects of YP 12, A Newly Synthesized Obovatol Derivative on Rat Aortic Vascular Smooth Muscle Cell Proliferation

  • Lim, Yong;Lee, Mi-Yea;Jung, Jae-Kyung;Pyo, Myoung-Yun;Yun, Yeo-Pyo
    • Journal of Food Hygiene and Safety
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    • v.26 no.3
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    • pp.187-191
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    • 2011
  • Platelet derived growth factor (PDGF)-BB is one of the most potent vascular smooth muscle cell(VSMC) proliferative factors, and abnormal VSMC proliferation by PDGF-BB plays an important role in the development and progression of atherosclerosis. The aim of this study was to assess the effect of YP 12, a newly synthesized obovatol derivative, on the proliferation of PDGF-BB-stimulated rat aortic VSMCs. The anti-proliferative effects of YP 12 on rat aortic VSMCs were examined by direct cell counting and by using $[^3H]$ thymidine incorporation assays. It was found that YP 12 potently inhibited the growth of VSMCs. The pre-incubation of YP 12 (1-4 ${\mu}M$) significantly inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated rat aortic VSMCs in a concentration-dependent manner. In accordance with these findings, YP 12 revealed blocking of the PDGF-BB-inducible progression through G0/G1 to S phase of the cell cycle in synchronized cells. Whereas, YP 12 did not show any cytotoxicity in rat aortic VSMCs in this experimental condition by WST-1 assay. These results also show that YP 12 may have potential as an anti-proliferative agent for the treatment of restenosis and atherosclerosis.

Synthesis of 1,6-Disubstituted 4,5,6,7-Tetrahydropyrazolo[3,4-c]pyridin-7-one Derivatives and Evaluation of Their Anticancer Activity

  • Devegowda, Vani Nelamane;Seo, Seon-Hee;Pae, Ae Nim;Nam, Ghil-Soo;Choi, Kyung-Il
    • Bulletin of the Korean Chemical Society
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    • v.33 no.2
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    • pp.647-650
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    • 2012
  • Promising anticancer compounds of the type 1,6-disubstituted 4,5,6,7-tetrahydropyrazolo[3,4-c]pyridin-7-ones were identified. The target compounds were readily synthesized in a large scale via a sequence of reactions starting from the commercially available primary amines. Their in vitro anti-proliferative activity has been evaluated on prostate (DU-145), colon (HT-29 and HCT-116) and melanoma (A375P) human cancer cell lines. The relationships between the structure and the anticancer activity, covering all tested cancer cell lines, revealed that the compound 5c with 2,4-dimethylphenyl substituent at $R^2$ was the most potent with the $IC_{50}$ values in the range as low as 0.16 to $0.40{\mu}M$.