• Toxicological Research
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• v.19 no.3
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• pp.197-203
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• 2003

Apicidin, a histone-deacetylase inhibitor, has been successfully used to inhibit the growth of cancer cells. In this study, the apoptotic potential and mechanistic insights of apicidin were investigated in human myeloid leukemia U937 cells. Treatment of U937 cells with apicidin resulted in a decrease of cell viability with apoptotic characteristics, including chromatin condensation and ladder-pattern fragmentation of genomic DNA. Apicidin converted the procaspase-3 protease to catalytically active effector protease, resulting in subsequent cleavage of poly (ADP-ribose) polymerase (PARP) and inhibitor of caspase-activated deoxyribonuclease (ICAD). In addition, apicidin induced the activation of caspase-9 protease and the cytosolic release of mitochondrial cytochrome c with mitochon-drial membrane potential transition. Moreover, apicidin transiently increased the expression of Fas and Fas ligand proteins. Taken together, the results suggest that apicidin induces apoptosis of U937 cells through activation of intrinsic caspase cascades and Fas/FasL system with mitochondrial dysfunction.

• Asian Journal of Innovation and Policy
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• v.6 no.1
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• pp.1-22
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• 2017

The essence of inclusive innovation is to serve poor, marginalized and underprivileged sections of society to improve their livelihoods and enable them to climb up the socio-economic ladder. In this article, we explore the contemporary Indian landscape. There is a diversity of institutions and institutional approaches, multiple methodologies and goals in promoting inclusive innovations in this landscape. There are grassroots innovation institutions. All these institutions and groups have demonstrated how to improve the living conditions of poor people and enhance their income. They have developed different methodologies of inclusive innovation to intervene, build capacities and capabilities of poor people towards bridging informal and formal sectors of economy. Indian landscape can now boast of some successful models and a "social laboratory" for inclusive innovation. The challenge, however, remains to replicate and multiply these models to impact other sectors of Indian informal economy.

• Asian Journal of Innovation and Policy
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• v.6 no.2
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• pp.170-191
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• 2017

Inclusive innovation refers to different types and forms of innovation activities or performance by which we can get more for lesser cost and which could cater and meet the needs and demands of more people. The essence of inclusive innovation is to help poor, marginalized and underprivileged sections of society to improve their livelihoods and enable them to climb up the socio-economic ladder. In the current phase of economic slowdown, increasing unemployment and inequalities, World Bank, OECD and various governments are turning towards inclusive innovation as a new source of optimism or even as a new innovation strategy. Whilst it is being reframed or packaged as a novel or a new strategy, one can trace its historical roots to the AT movement and the Gandhian ideas of economy and society in the 1940s and 1950s. These ideas have inspired and influenced a range of individuals, institutions and civil society groups in inclusive innovation.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.90.2-90.2
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• 2003

In a continuous effort to develop novel anticancer agents we newly synthesized and evaluated the antitumor activity of nucleoside analogues. One analogue, 4-[2-Chlor-6-(3-iodo-benzylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentanecarboxylic acid methylamide (LJ-331), has been shown to exert a potent inhibition of human cancer cell growth in vitro including human lung (A549), stomach (SNU-638) and leukemia (HL-60) cancer cells. Following mechanism of action study revealed that LJ-331 induces cell cycle arrest at the G$_1$ phase in HL-60 cells and evokes apoptotic phenomena such as an increase in DNA ladder intensity and chromatin condensation by a dose-and time-dependent manner. (omitted)

• Journal of Ginseng Research
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• v.31 no.1
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• pp.1-13
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• 2007

We found that the main bacterial metabolite M1 is an active component of orally administered protopanxadiol-type ginsenosides, and that the anti-metastatic effect by oral administration of ginsenosides may be primarily mediated through the inhibition of tumor invasion, migration and growth of tumor cells by their metabolite M1. Pharmacokinetic study after oral administration of ginsenoside Rb1 revealed that M1 was detected in serum for 24 h by HPLC analysis but Rb1 was not detected. M1, with anti-metastatic property, inhibited the proliferation of murine and human tumor cells in a time- and concentration-dependent manner in vitro, and also induced apoptotic cell death (the ladder fragmentation of the extracted DNA). The induction of apoptosis by M1 involved the up-regulation of the cyclin-dependent kinase(CDK) inhibitor $p27^{Kip1}$ as well as the down-regulation of a proto-oncogene product c-Myc and cyclin D1 in a time-dependent manner. Thus, M1 might cause the cell-cycle arrest (G1 phase arrest) in honor cells through the up/down-regulation of these cell-growth related molecules, and consequently induce apoptosis. The nucleosomal distribution of fluorescence-labeled M1 suggests that the modification of these molecules is induced by transcriptional regulation. Tumor-induced angiogenesis (neovascularization) is one of the most important events concerning tumor growth and metastasis. Neovascularization toward and into tumor is a crucial step for the delivery of nutrition and oxygen to tumors, and also functions as the metastatic pathway to distant organs. M1 inhibited the tube-like formation of hepatic sinusoidal endothelial (HSE) cells induced by the conditioned medium of colon 26-L5 cells in a concentration-dependent manner. However, M1 at the concentrations used in this study did not affect the growth of HSE cells in vitro.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.599-607
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• 2017

Most normal cells express L-type amino acid transporter 2 (LAT2). However, L-type amino acid transporter 1 (LAT1) is highly expressed in many tumor cells and presumed to support their increased growth and proliferation. This study examined the effects of JPH203, a selective LAT1 inhibitor, on cell growth and its mechanism for cell death in Saos2 human osteosarcoma cells. FOB human osteoblastic cells and Saos2 cells expressed LAT1 and LAT2 together with their associating protein 4F2 heavy chain, but the expression of LAT2 in the Saos2 cells was especially weak. JPH203 and BCH, a non-selective L-type amino acid transporter inhibitor, potently inhibited L-leucine uptake in Saos2 cells. As expected, the intrinsic ability of JPH203 to inhibit L-leucine uptake was far more efficient than that of BCH in Saos2 cells. Likewise, JPH203 and BCH inhibited Saos2 cell growth with JPH203 being superior to BCH in this regard. Furthermore, JPH203 increased apoptosis rates and formed DNA ladder in Saos2 cells. Moreover, JPH203 activated the mitochondria-dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bad, Bax, and Bak, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. These results suggest that the inhibition of LAT1 activity via JPH203, which may act as a potential novel anti-cancer agent, leads to apoptosis mediated by the mitochondria-dependent intrinsic apoptotic signaling pathway by inducing the intracellular depletion of neutral amino acids essential for cell growth in Saos2 human osteosarcoma cells.

• YAKHAK HOEJI
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• v.52 no.1
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• pp.1-6
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• 2008

The present study investigated the antiproliferative effects of Crnum asiaticum var. japonicum against HL-60 human leukemia cells. The 80% MeOH extract or several solvent fractions from the C. asiaticum inhibited the growth of HL-60 cells, whereas the growth of HEL-299 cells, human embryonic lung fibroblast, was scarcely inhibited. When the HL-60 cells were treated with the $CHCl_3$ fraction, the BuOH fraction, the EtOAc fraction and the $H_2O$ fraction, DNA ladder, chromatin condensation and increase of sub-G1 hypodiploid cells were observed. Furthermore, the $CHCl_3$ fraction and the BuOH fraction reduced Bc1-2 mRNA level, whereas Bax mRNA level was increased. These results suggest that the inhibitory effect of C. asiaticum on the growth of the HL-60 cell might be mediated through the induction of apoptosis via the down-regulation of Bc1-2. Taken together, components of C. asiaticum might have a therapeutic potential for the treatment of human leukemia.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.5
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• pp.555-560
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• 2008

Amino acid transporters are essential for the growth and proliferation in all living cells. Among the amino acid transporters, the system L amino acid transporters are the major nutrient transport system responsible for the $Na^+$-independent transport of neutral amino acids including several essential amino acids. The L-type amino acid transporter 1 (LAT1), an isoform of system L amino acid transporter, is highly expressed in cancer cells to support their continuous growth and proliferation. 2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) is a model compound for the study of amino acid transporter as a system L selective inhibitor. We have examined the effect and mechanism of BCH on cell growth suppression in HEp2 human head and neck squamous cell carcinoma. The BCH inhibited the L-leucine transport in a concentration-dependent manner with a $IC_{50}$ value of $51.2{\pm}3.8{\mu}M$ in HEp2 cells. The growth of HEp2 cells was inhibited by BCH in the timeand concentration-dependent manners. The formation of DNA ladder was not observed with BCH treatment in the cells. Furthermore, the proteolytic processing of caspase-3 and caspase-7 in the cells were not detected by BCH treatment. These results suggest that the BCH inhibits the growth of HEp2 human head and neck squamous cell carcinoma through the intracellular depletion of neutral amino acids for cell growth without apoptotic processing.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.3
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• pp.437-443
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• 2003

Epidemiological data suggest that lycopene has anticancer activities in humans. Insulin-like growth factor-I receptor (IGF-IR) is a transmembrane tyrosine kinase that mediates the biological actions of IGFs and may play an active role in cancer progression. Because our previous in vitro studies have indicated lycopene inhibits HT-29 cell growth, the aim of this study was to determine whether lycopene induces apoptotic cell death and the inhibitory effect of lycopene on HT-29 cell growth is related to changes in IGF-IR levels and the receptor's intracellular signalling pathways. HT-29 cells were incubated for 4 days in serum-free medium in the presence of 0, 25, 50, or 100 $\mu$M lycopene, and the DNA fragmentation assay was performed. Cells treated with lycopene produced a distinct oligonucleosomal ladder with different sizes of DNA fragments, a typical characteristic of cells undergoing apoptosis. HT-29 cells were cultured for 4 days in serum-free medium in the presence of 0~100 $\mu$M lycopene and IGF-I (10nM) was added for 0~60 minutes immediately prior to lysate preparations. Western blot analysis of total lysates revealed that lycopene decreased the levels of IRS-1, Akt, phosphatidylinositol 3-kinase (PI3K), and IGF-IR $\beta$-subunit, and increased the levels of the IGF-IR precursor dose dependently. Lycopene also decreased IGF-I-induced phosphorylation of IGF-IR$\beta$, IRS-1 and Akt, which were, at least in part, due to decreased expression of these proteins. These results suggest that lycopene induces apoptosis of HT-29 cells by inhibiting IGF-IR signaling thereby interfering with an IGF-II-driven autocrine growth loop, which is known to exist in this cell line.

• Animal Systematics, Evolution and Diversity
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• v.23 no.1
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• pp.35-38
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• 2007

Two new sponges, Euryspongia coreana n, sp, and E. regularis n, sp., collected from Hataedo, Ulleungdo and Chujado, Korea by SCUBA diving during the period from 2001 to 2005. Euryspongia coreana n. sp, is very close to E. lactea Row, 1911 and E. arenaria Bergquist, 1961 in skeletal structure, but primary and secondary fibres of the new species are thicker than those of E. lactea, E. arenaria is cored with mostly spicule fragments but E. coreana n. sp. is cored with mainly sand. E. regularis n. sp. is readily distinguished from other eurypsongian sponges. by its thickly encrusting growth form, yellowish ivory colour, and thickness of fibres. The bright yellow color and regular ladder-like skeletal structure are major features distinguishing this E. regularis n. sp. from other euryspongian sponges. Most species are brown, violet, red or orange in color except for E. lactea (milky white), E. arenaria (biscuit) and E. coreana n. sp. (yellowish ivory). Other euryspongian sponges have regularly or irregularly well developed secondary fibres, but E. regularis n. sp. has simple and regular secondary fibres.