• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.4
• /
• pp.2201-2205
• /
• 2013

Colorectal cancer (CRC) is one of the most common cancers in many parts of the world. Its development is a multi-step process involving three distinct stages, initiation that alters the molecular message of a normal cell, followed by promotion and progression that ultimately generates a phenotypically altered transformed malignant cell. Reports have suggested an association of the phosphoinositide-3-kinase (PI3K)/Akt pathway with colon tumorigenesis. Activation of Akt signaling and impaired expression of phosphatase and tensin homolog (PTEN) (a negative regulator of Akt) has been reported in 60-70% of human colon cancers and inhibitors of PI3K/Akt signaling have been suggested as potential therapeutic agents. Around 80% of human colon tumors possess mutations in the APC gene and half of the remainder feature ${\beta}$-catenin gene mutations which affect downstream signaling of the PI3K/Akt pathway. In recent years, there has been a great focus in targeting these signaling pathways, with natural and synthetic drugs reducing the tumor burden in different experiment models. In this review we survey the role of PI3K/Akt/mTOR and Wnt signaling in CRC.

• Molecules and Cells
• /
• v.21 no.2
• /
• pp.294-301
• /
• 2006

We have previously reported that phosphorylation of eukaryotic elongation factor 2 (eEF2) is related to the differentiation of chick embryonic muscle cells in culture. In the present study, we found that eEF2 phosphorylation declined shortly after induction of differentiation of L6 myoblasts, when the cells prepare for terminal differentiation by withdrawing from the cell cycle. This decrease in phosphorylation was prevented by inhibitors of phosphoinositide 3-kinase (PI3-kinase) that strongly inhibit myoblast differentiation. We hypothesized that PI3-kinase plays an important role in myoblast differentiation by regulating eEF2 phosphorylation in the early stages of differentiation. To test this hypothesis, myoblasts were synchronized at in $G_2/M$ and cultured in fresh differentiation medium (DM) or growth medium (GM). In DM the released cells accumulated in $G_0$/$G_1$ while in GM they progressed to S phase. In addition, cyclin D1 was more rapidly degraded in DM than in GM, and eEF2 phosphorylation decreased more. Inhibitors of PI3-kinase increased eEF2 phosphorylation, but PI3-kinase became more activated when eEF2 phosphorylation declined. These results suggest that the regulation of L6 myoblast differentiation by PI3-kinase is related to eEF2 phosphorylation.

• Development and Reproduction
• /
• v.4 no.1
• /
• pp.29-35
• /
• 2000

A phosphatidylinositol 3-kinase (PI3K) is a upstream component of insulin signaling by which protein synthesis can be stimulated in many systems. To elucidate involvement of PI3K and its downstream mammalian target of rapamycin (mTOR) in the insulin signaling in pleimplantation mouse embryos, 8-cell embryos were cultured to blastocysts in the presence or absence of insulin and／or inhibitor drugs. The number of blastomeres per blastocyst, protein synthesis, and protein phosphorylation were examined. There was significant difference in embryonic development to blastocyst stage and hatching was potentiated by the insulin supplementation. The increase in the mean celt numbers per blastocyst was apparent in the insulin culture. Wortmannin, a PI3K inhibitor and rapamycin, an inhibitor of mTOR abolished the stimulatory effect of insulin on morphological development mitosis and protein synthesis. In autoradiography, phosphoproteins pp22 and pp30 which undergo phosphorylation in response to insulin were identified. Taken together, it can be suggested that PI3K and mTOR engaged in insulin signaling in the mouse embryo 8-cell onward and mediate embryotropic offset of insulin.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.45 no.6
• /
• pp.835-842
• /
• 2016

The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway plays a crucial role in cancer occurrence by promoting cell proliferation and inhibiting apoptosis. In the present study, we evaluated the effect of a PI3K inhibitor, LY294002, on the chemosensitivity of gastric cancer cells to cordycepin, a predominant functional component of the fungus Cordyceps militaris, in AGS human gastric cancer cells and investigated possible underlying cellular mechanisms. Our results revealed that cordycepin inhibited viability of AGS cells in a concentration-dependent manner and induced apoptosis, as determined by apoptotic cell morphologies and fluorescence-activated cell sorting analysis associated with attenuated activation of the PI3K/Akt signaling pathway. Treatment with cordycepin in combination with a subtoxic concentration of LY294002 enhanced cordycepin-induced cytotoxicity and apoptotic potentials in AGS cells. Sensitization of LY294002 to cordycepin-induced apoptosis was accompanied by activation of caspases (caspases-3, -8, and -9) and was concomitant with poly(ADP-ribose) polymerase cleavage. Moreover, LY294002 up-regulated pro-apoptotic Bax and enhanced truncation of Bid in cordycepin-treated AGS cells, which was connected with increased loss of mitochondrial membrane potential and release of cytochrome c from mitochondria to the cytosol. Taken together, these results indicate that inhibition of the PI3K/Akt signaling pathway could augment cordycepin-induced apoptosis in human gastric cancer cells by up-regulating caspase activity through mitochondrial dysfunction.

• 한국정보디스플레이학회:학술대회논문집
• /
• 2004.08a
• /
• pp.903-906
• /
• 2004

A ${\pi}$ cell is initially in splay state. Before driving a ${\pi}$ cell, transition from splay to bend state is always necessary which originates from nucleation. We propose a novel technique to make bend transition fast and effectively by forming transition cores around the pixels with the technique of multi-domain alignment, where domain boundaries play a crucial role in splay to bend transition. This noble technique enables the splay to bend transition to occur within less than 2 seconds with a low applied voltage.

• BMB Reports
• /
• v.30 no.3
• /
• pp.182-187
• /
• 1997

The NADPH oxidase of phagocytes catalyzes the reduction of oxygen to $O_2^-$ at the expense of NADPH. The enzyme is dormant in resting neutrophils and becomes activated on stimulation. During activation, $p47^{phox}\;(\underline{ph}agocyte\;\underline{ox}idase\;factor)$, a cytosolic oxidase subunit, becomes extensively phosphorylated at a number of serines located between S303-S379. Oxidase activation can also be achieved by the addition of phosphorylated recombinant $p47^{phox}$ by protein kinase C in the cell-free system in the presence of $GTP{\gamma}S$. The cell-free activation is inhibited by wortmannin and LY294002. specific inhibitors of phosphatidylinositol 3kinase (PI 3-kinasel) These results indicate that PI 3-kinase may playa pivotal role in the activation of NADPH oxidase.

• Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
• /
• 2004.05a
• /
• pp.206-209
• /
• 2004

We investigated response characteristics of liquid crystal display(LCD) with different operating mode of nematic liquid crystals (NLCs) such as $45^{\circ}$twist nematic (TN), $67.3^{\circ}$TN and ECB(electrical controlled birefringence) on a rubbed polyimide (PI) surface. The three kinds of LCD operating mode obtain stable EO performance. Low transmittances of the $45^{\circ}$TN and $67.3^{\circ}$TN cell on the rubbed PI surface were achieved by using low cell gap d. The fast response time of ECB cell among the three kinds of LCD operating mode was measured.

• Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
• /
• 1998.06a
• /
• pp.271-274
• /
• 1998

In this paper, the monodomain alignment of nematic liquid crystal(NLC) in the cell fabricated by one side transcription alignment method on PI surface with side chain were investigated. The LC alignment produced by the transcription alignment method is attributable to a memory effect of the NLC on Pl surfaces. We observed that the pretilt angle of NLC is generated about 3.6$^{\circ}$ in a cell with one side transcription alignment on PI surface. Also, the electro-optical(EO) performance of TN-LCD with one side transcription alignment method on PI surface will be discussed.

• Journal of Information Display
• /
• v.5 no.2
• /
• pp.19-22
• /
• 2004

A ${\pi}$ cell is initially in splay state. Before driving a ${\pi}$ cell, transition from splay to bend state is always necessary which originates from nucleation. We propose a novel technique to make bend transition fast and effectively by forming transition cores around the pixels with the technique of multi-domain alignment, where domain boundaries play a crucial role in splay to bend transition. This noble technique enables the splay to bend transition to occur within less than 2 seconds with a low applied voltage.

• Archives of Pharmacal Research
• /
• v.22 no.2
• /
• pp.108-112
• /
• 1999

Recombinant murine stem cell factor (rmSCF) or recombinant murine nerve growth factor (rmNGF) induced the morphological change of large numbers of rat peritoneal mast cells (RPMC). We investigated the role of phosphatidylinositol $3^{l}-kinase$ (PI3-kinase) in receptors-mediated morphological change in RPMC. Exposure of RPMC to PI3-kinase inhibitor, wortmannin, before the addition of rmSCF and rmNGF antagonized those factors-induced morphological change. These results suggest that the PI3-kinase is involved in the signal transduction pathway responsible for morphological change following stimulation of rmSCF and rmNGF and that wortmannin blocks these responses.