Protein Information

Name phosphatidylinositol 3 kinase (protein family or complex)
Synonyms PI3 kinase; PI3 kinases; PI3K; Phosphatidylinositol 3 kinase; Phosphatidylinositol 3 kinases; Phosphatidylinositol 4,5 bisphosphate 3 kinase; Phosphatidylinositol 4,5 bisphosphate 3 kinases

Compound Information

Name cycloheximide
CAS

Reference List

PubMed Abstract RScore(About this table)
17032741 Finlay D, Ruiz-Alcaraz AJ, Lipina C, Perrier S, Sutherland C: A temporal switch in the insulin-signalling pathway that regulates hepatic IGF-binding protein-1 gene expression. J Mol Endocrinol. 2006 Oct;37(2):227-37.


We havepreviously shownthat the insulin regulationof hepatic IGF-binding protein-1 (IGFBP1) expression requiresthe signalling proteins phosphatidylinositol 3-kinase (PI 3-kinase) and mammalian target of rapamycin (mTOR).
1(0,0,0,1) Details
16545883 Lee GC, Yi HA, Lee CH: Stimulation of interferon-beta gene expression by human cytomegalovirus via nuclear factor kappa B and phosphatidylinositol 3-kinase pathway. Virus Res. 2006 May;117(2):209-14. Epub 2006 Mar 20.

Stimulation of IFN-beta by HCMV infection was not blocked by cycloheximide, an inhibitor of protein synthesis, further suggesting that the expression of HCMV genes is not required for the stimulation of IFN-beta gene transcription.
1(0,0,0,1) Details
18973758 Frey MR, Edelblum KL, Mullane MT, Liang D, Polk DB: The ErbB4 growth factor receptor is required for colon epithelial cell survival in the presence of TNF. Gastroenterology. 2009 Jan;136(1):217-26. Epub 2008 Sep 25.

ErbB4 siRNA sensitized cells to TNF-stimulated apoptosis, while over expression blocked apoptosis induced by TNF plus cycloheximide.
Inhibition of the phosphatidylinositol 3-kinase/Akt signaling cascade reversed the ability of ErbB4 over expression to protect from cytokine-induced apoptosis.
1(0,0,0,1) Details
15671029 Vertino AM, Bula CM, Chen JR, Almeida M, Han L, Bellido T, Kousteni S, Norman AW, Manolagas SC: Nongenotropic, anti-apoptotic signaling of 1alpha,25 (OH) 2-vitamin D3 and analogs through the ligand binding domain of the vitamin D receptor in osteoblasts and osteocytes. J Biol Chem. 2005 Apr 8;280(14):14130-7. Epub 2005 Jan 25.

Finally, actinomycin D or cycloheximide prevented the anti-apoptotic effect of 1alpha,25 (OH) 2D3, indicating that transcriptional events are also required.
The anti-apoptotic effects of 1alpha,25 (OH) 2D3 and the 6-s-cis-locked 1alpha,25 (OH) 2-lumisterol3 analog in calvaria cells were blocked by three cytoplasmic kinase inhibitors: Src kinase inhibitor 4-amino-5-(4-methylphenyl)-7-(t-butyl) pyrazolo [3,4-d] pyrimidine (PP1), phosphatidylinositol 3 kinase inhibitor Wortmannin, and the JNK kinase inhibitor SP600125.
1(0,0,0,1) Details
20352620 Lorente-Cebrian S, Bustos M, Marti A, Martinez JA, Moreno-Aliaga MJ: Eicosapentaenoic acid up-regulates apelin secretion and gene expression in 3T3-L1 adipocytes. Mol Nutr Food Res. 2010 Mar 29.

EPA also stimulated Akt phosphorylation, a down-stream target of phosphatidylinositol 3-kinase (PI3K), in 3T3-L1 adipocytes.
Furthermore, the stimulatory effect of EPA on basal apelin release was also observed in the presence of Actinomycin D and Cycloheximide, suggesting that EPA might also regulate apelin secretion by via post-transcriptional mechanisms.
1(0,0,0,1) Details
19193945 Soria LR, Gradilone SA, Larocca MC, Marinelli RA: Glucagon induces the gene expression of aquaporin-8 but not that of aquaporin-9 water channels in the rat hepatocyte. Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R1274-81. Epub 2009 Feb 4.

Cycloheximide also showed no effect, suggesting that glucagon-induced AQP8 expression does not depend on protein synthesis but rather on protein degradation.
The action of glucagon on hepatocyte AQP8 was mimicked by dibutyryl cAMP and suppressed by PKA or phosphatidylinositol-3-kinase (PI3K) inhibitors.
1(0,0,0,1) Details
19473970 Ding B, Kirkiles-Smith NC, Pober JS: FOXO3a regulates oxygen-responsive expression of tumor necrosis factor receptor 2 in human dermal microvascular endothelial cells. J Biol Chem. 2009 Jul 17;284(29):19331-9. Epub 2009 May 27.


Hypoxia leads to FOXO3a phosphorylation at an Akt/protein kinase B target site and subsequent nuclear export; these processes are reversed by reoxygenation and blocked by LY294002, a phosphatidylinositol 3-kinase inhibitor that blocks Akt activation.
1(0,0,0,1) Details
15753078 Arbel-Goren R, Levy Y, Ronen D, Zick Y: Cyclin-dependent kinase inhibitors and JNK act as molecular switches, regulating the choice between growth arrest and apoptosis induced by galectin-8. J Biol Chem. 2005 May 13;280(19):19105-14. Epub 2005 Mar 7.

Accordingly, SP600125, the inhibitor of JNK, and wortmannin, the inhibitor of phosphatidylinositol 3-kinase, which is the upstream activator of PKB, inhibited the increase in the cellular content of p21.
When p21 expression was inhibited by cycloheximide, galectin-8 directed the cells toward apoptosis, which involves induction of poly (ADP-ribose) polymerase cleavage.
1(0,0,0,1) Details
19396617 Carraro-Lacroix LR, Girardi AC, Malnic G: Long-term regulation of vacuolar H (+)-ATPase by angiotensin II in proximal tubule cells. Pflugers Arch. 2009 Sep;458(5):969-79. Epub 2009 Apr 26.


Inhibition of phosphatidylinositol-3-kinase (PI3K) by wortmannin and of p38 mitogen-activated protein kinase (MAPK) by SB 203580 also blocked this effect.
1(0,0,0,1) Details
17989348 Papineni S, Chintharlapalli S, Safe S: Methyl 2-cyano-3,11-dioxo-18 beta-olean-1,12-dien-30-oate is a peroxisome proliferator-activated receptor-gamma agonist that induces receptor-independent apoptosis in LNCaP prostate cancer cells. Mol Pharmacol. 2008 Feb;73(2):553-65. Epub 2007 Nov 7.

However, induction of these responses by beta-CDODA-Me was PPARgamma-independent and due to activation of phosphatidylinositol-3-kinase, mitogen-activated protein kinase, and jun N-terminal kinase pathways by this compound.
In contrast, beta-CDODA-Me also decreased androgen receptor (AR) and prostate-specific antigen (PSA) mRNA and protein levels through kinase-independent pathways. beta-CDODA-Me repressed AR mRNA transcription, whereas decreased PSA mRNA levels were dependent on protein synthesis and were reversed by cycloheximide.
1(0,0,0,1) Details
19071214 Lee BS, Park M, Cha HY, Lee JH: Hepatocyte growth factor induces delayed STAT3 phosphorylation through interleukin-6 expression. Cell Signal. 2009 Mar;21(3):419-27. Epub 2008 Nov 30.

Blocking of the phosphorylation by cycloheximide or actinomycin D and the rapid STAT3 phosphorylation with the conditioned medium from HGF/SF-treated NIH3T3 cells suggested that a newly synthesized secretory protein was responsible for the delayed STAT3 phosphorylation.
Collectively, these results demonstrate that HGF/SF-Met signal cascade stimulates IL-6 production via PI3 kinase pathway, leading to STAT3 phosphorylation as a secondary effect.
1(0,0,0,1) Details
15965068 Hou CC, Hung SL, Kao SH, Chen TH, Lee HM: Celecoxib induces heme-oxygenase expression in glomerular mesangial cells. Ann N Y Acad Sci. 2005 May;1042:235-45.

On the other hand, LY 294002, a phosphatidylinositol 3-kinase (PI-3K)-specific inhibitor, prevented the enhancement of HO-1 expression.
Celecoxib-induced HO-1 protein expression was inhibited by actinomycin D and cycloheximide, suggesting that de novo transcription and translation are required in this process.
1(0,0,0,1) Details
17015939 Purintrapiban J, Suttajit M, Forsberg NE: Differential activation of glucose transport in cultured muscle cells by polyphenolic compounds from Canna indica L. Biol Pharm Bull. 2006 Oct;29(10):1995-8.

Our findings suggest that GLUT1 protein synthesis and the activation of phosphatidylinositol 3-kinase (PI3K) are critical for the increase in glucose transporter activity at the plasma membrane and essential for the maximal induction of glucose transport by CI in L8 muscle cells.
Cycloheximide treatment almost completely reversed CI-induced 2-DG uptake to the basal level.
1(0,0,0,1) Details
18638274 Shao H, Yi XM, Wells A: Epidermal growth factor protects fibroblasts from apoptosis via PI3 kinase and Rac signaling pathways. Wound Repair Regen. 2008 Jul-Aug;16(4):551-8.

Interestingly, EGF prevention of apoptosis induced by tumor necrosis factor-alpha in the face of cycloheximide blockade of protein translation occurs via a different set of pathways as the simultaneous inhibition of extracellular signal-regulated kinase, Rac, and PI3K signaling did not eliminate EGF from rescuing fibroblasts in the face of this cytokine.
1(0,0,0,1) Details
15642371 Schnitzer SE, Schmid T, Zhou J, Eisenbrand G, Brune B: Inhibition of GSK3beta by indirubins restores HIF-1alpha accumulation under prolonged periods of hypoxia/anoxia. FEBS Lett. 2005 Jan 17;579(2):529-33.


HIF-1alpha is subjected to proteasomal destruction or enhanced protein translation, which requires the phosphatidylinositol 3-kinase (PI3K)/Akt pathway.
1(0,0,0,1) Details
17615150 Lamirand A, Mercier G, Ramauge M, Pierre M, Courtin F: Hypoxia stabilizes type 2 deiodinase activity in rat astrocytes. . Endocrinology. 2007 Oct;148(10):4745-53. Epub 2007 Jul 5.

Specific inhibitors of ERK, p38 MAPK, or phosphatidylinositol 3-kinase pathways were without any effect on hypoxia-increased D2 activity, eliminating their role in the effects of hypoxia.
Cycloheximide did not block the effect of hypoxia on D2 activity and D2 half-life was enhanced under hypoxia demonstrating a posttranslational action of hypoxia.
1(0,0,0,1) Details
15714461 Shi YH, Wang YX, Bingle L, Gong LH, Heng WJ, Li Y, Fang WG: In vitro study of HIF-1 activation and VEGF release by bFGF in the T47D breast cancer cell line under normoxic conditions: involvement of PI-3K/Akt and MEK1/ERK pathways. J Pathol. 2005 Mar;205(4):530-6.

The data show that HIF-1alpha expression is induced by bFGF in a dose- and time-dependent fashion, while increased HIF-1alpha protein expression and transactivity of HIF-1 are due to the phosphorylation of Akt by bFGF, as indicated by application of the phosphatidylinositol 3-kinase (PI-3K) inhibitor LY294002.
In addition, the translation inhibitor cycloheximide confirmed that bFGF-induced HIF-1alpha protein expression was due to de novo protein synthesis.
1(0,0,0,1) Details
17259394 Mariappan MM, Feliers D, Mummidi S, Choudhury GG, Kasinath BS: High glucose, high insulin, and their combination rapidly induce laminin-beta1 synthesis by regulation of mRNA translation in renal epithelial cells. Diabetes. 2007 Feb;56(2):476-85.

Cycloheximide, but not actinomycin-D, abrogated increased laminin-beta1 synthesis.
High glucose, high insulin, and high glucose+high insulin stimulated phosphorylation of 4E-BP1, a repressor binding protein for eukaryotic initiation factor 4E (eIF4E), that was dependent on activation of phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin.
1(0,0,0,1) Details
17331500 Bian ZM, Elner SG, Elner VM: Regulation of VEGF mRNA expression and protein secretion by TGF-beta2 in human retinal pigment epithelial cells. Exp Eye Res. 2007 May;84(5):812-22. Epub 2007 Jan 9.

Moreover, TGF-beta2-induced RPE VEGF secretion was significantly reduced by inhibitors of mitogen-activated protein (MAP) kinase (MEK) (U0126), p38 (SB202190), c-Jun NH2-terminal kinase (JNK), Sp600125, protein tyrosine kinase (PTK) (Genistein), and phosphatidylinositol 3-kinase (PI3K) (Ly294002).
Stimulation of VEGF expression by TGF-beta2 was blocked by cycloheximide, suggesting that de novo protein synthesis is required.
1(0,0,0,1) Details
19664126 Misiak-Tloczek A, Brzezinska-Blaszczyk E: IL-6, but not IL-4, stimulates chemokinesis and TNF stimulates chemotaxis of tissue mast cells: involvement of both mitogen-activated protein kinases and phosphatidylinositol 3-kinase signalling pathways. APMIS. 2009 Aug;117(8):558-67.


We also documented that the migration response of mast cells to stimulation with IL-6 and TNF was mediated through signal transduction pathways involving mitogen-activated protein kinases and phosphatidylinositol 3-kinase.
1(0,0,0,1) Details
19684181 McEwen ST, Balus SF, Durand MJ, Lombard JH: Angiotensin II maintains cerebral vascular relaxation via EGF receptor transactivation and ERK1/2. Am J Physiol Heart Circ Physiol. 2009 Oct;297(4):H1296-303. Epub 2009 Aug 14.

The protective effect of ANG II infusion to restore vascular relaxation was eliminated by coinfusion of either the EGF receptor kinase inhibitor AG-1478 (20 microg/h), the ERK1/2 inhibitor PD-98059 (10 microg/h), or the protein synthesis inhibitor cycloheximide (5 microg/h).
In ANG II-infused rats fed HS diet, and in rats fed LS diet, vasodilator responses to reduced PO (2) and iloprost were unaffected by the p38 MAP kinase inhibitor SB-203580 and the phosphatidylinositol 3-kinase inhibitor wortmannin.
1(0,0,0,1) Details
19254925 Maeda T, Horiuchi N: Simvastatin suppresses leptin expression in 3T3-L1 adipocytes via activation of the cyclic AMP-PKA pathway induced by inhibition of protein prenylation. J Biochem. 2009 Jun;145(6):771-81. Epub 2009 Mar 2.

Treatment with phosphatidylinositol 3-kinase (PI3K) inhibitors, LY294002 and wortmannin, reduced leptin expression in 3T3-L1 cells.
Simvastatin inhibition of leptin gene transcription was not abrogated by pre-treatment with cycloheximide, an inhibitor of protein synthesis.
1(0,0,0,1) Details
16531089 Mukherjee D, Mukherjee D, Sen U, Paul S, Bhattacharyya SP: In vitro effects of insulin-like growth factors and insulin on oocyte maturation and maturation-inducing steroid production in ovarian follicles of common carp, Cyprinus carpio. Comp Biochem Physiol A Mol Integr Physiol. 2006 May;144(1):63-77. Epub 2006 Mar 10.

Cycloheximide was shown to inhibit the induction of GVBD and DHP production by IGF-I, b-insulin and HCG.
Inhibitors of phosphatidylinositol-3 kinase (PI-3 kinase), wortmannin and LY294002 inhibited GVBD by IGF-I and b-insulin.
1(0,0,0,1) Details
17804721 Endo H, Murata K, Mukai M, Ishikawa O, Inoue M: Activation of insulin-like growth factor signaling induces apoptotic cell death under prolonged hypoxia by enhancing endoplasmic reticulum stress response. Cancer Res. 2007 Sep 1;67(17):8095-103.

The cells were rescued from apoptosis when phosphatidylinositol 3-kinase (PI3K) or mTOR activity was inhibited, suggesting that these signals are critical in the observed cell death.
IGF-induced cell death under hypoxic conditions was prevented by treatment with cycloheximide, suggesting that de novo protein synthesis is required.
1(0,0,0,1) Details
17660326 Chachami G, Hatziefthimiou A, Liakos P, Ioannou MG, Koukoulis GK, Bonanou S, Molyvdas PA, Simos G, Paraskeva E: Exposure of differentiated airway smooth muscle cells to serum stimulates both induction of hypoxia-inducible factor-1{alpha} and airway responsiveness to ACh. Am J Physiol Lung Cell Mol Physiol. 2007 Oct;293(4):L913-22. Epub 2007 Jul 27.

Treatment with actinomycin D, cycloheximide, the phosphatidylinositol 3-kinase inhibitors LY-294002 and wortmannin or the reactive oxygen species scavenger diphenyleneiodonium inhibited the FBS-dependent induction of HIF-1alpha.
32(0,1,1,2) Details
17683115 Fernandez N, Gonzalez A, Valera I, Alonso S, Crespo MS: Mannan and peptidoglycan induce COX-2 protein in human PMN via the mammalian target of rapamycin. Eur J Immunol. 2007 Sep;37(9):2572-82.


Treatment with the phosphatidylinositol 3-kinase inhibitor (PI3K) wortmaninn, the mammalian target of rapamycin (mTOR) inhibitor rapamycin, and the translation inhibitor cycloheximide blocked the induction of COX-2 protein in response to mannan and PGN, whereas the transcriptional inhibitor actinomycin D did not show a significant effect.
0(0,0,0,0) Details
16251184 Almeida M, Han L, Bellido T, Manolagas SC, Kousteni S: Wnt proteins prevent apoptosis of both uncommitted osteoblast progenitors and differentiated osteoblasts by beta-catenin-dependent and -independent signaling cascades involving Src/ERK and phosphatidylinositol 3-kinase/AKT. J Biol Chem. 2005 Dec 16;280(50):41342-51. Epub 2005 Oct 25.

The anti-apoptotic effect of Wnt3a was abrogated by inhibitors of canonical Wnt signaling, as well as by inhibitors of MEK, Src, phosphatidylinositol 3-kinase (PI3K), or Akt kinases, or by the addition of cycloheximide to the culture medium.
31(0,1,1,1) Details
17557191 Shen J, Jiang J, Wei Y, Zhou L, Liu D, Zhou J, Gu J: Two specific inhibitors of the phosphatidylinositol 3-kinase LY294002 and wortmannin up-regulate beta1,4-galactosyltransferase I and thus sensitize SMMC-7721 human hepatocarcinoma cells to cycloheximide-induced apoptosis. Mol Cell Biochem. 2007 Oct;304(1-2):361-7. Epub 2007 Jun 8.
31(0,1,1,1) Details
18540098 Kawauchi K, Tobiume K, Iwashita K, Inagaki H, Morikawa T, Shibukawa Y, Moriyama Y, Hirata H, Kamata H: Cycloprodigiosin hydrochloride activates the Ras-PI3K-Akt pathway and suppresses protein synthesis inhibition-induced apoptosis in PC12 cells. Biosci Biotechnol Biochem. 2008 Jun;72(6):1564-70. Epub 2008 Jun 7.


In this study, we found a novel function of cPrG-HCl; to suppress cell death in PC12 cells, which is caused by protein synthesis inhibitors cycloheximide and actinomycin D. cPrG-HCl activated Akt and suppressed apoptosis, and this was accompanied by inhibition of caspase-3 activity and DNA fragmentation independently of its H (+)/Cl (-) symporter activity.
0(0,0,0,0) Details
15728510 Molnarfi N, Hyka-Nouspikel N, Gruaz L, Dayer JM, Burger D: The production of IL-1 receptor antagonist in IFN-beta-stimulated human monocytes depends on the activation of phosphatidylinositol 3-kinase but not of STAT1. J Immunol. 2005 Mar 1;174(5):2974-80.


The use of cycloheximide and actinomycin D shows that sIL-1Ra was an immediate early gene induced by IFN-beta and that PI3K was controlling sIL-1Ra gene transcription.
0(0,0,0,0) Details
15695798 Paik JY, Lee KH, Ko BH, Choe YS, Choi Y, Kim BT: Nitric oxide stimulates 18F-FDG uptake in human endothelial cells through increased hexokinase activity and GLUT1 expression. J Nucl Med. 2005 Feb;46(2):365-70.

SNP-stimulated (18) F-FDG uptake was abolished by cotreatment with cycloheximide, the tyrosine kinase inhibitor genistein, the phosphatidylinositol-3 kinase (PI3K) inhibitor wortmannin, or the protein kinase C inhibitor staurosporine.
31(0,1,1,1) Details
15659777 Boulday G, Fitau J, Coupel S, Soulillou JP, Charreau B: Exogenous tissue inhibitor of metalloproteinase-1 promotes endothelial cell survival through activation of the phosphatidylinositol 3-kinase/Akt pathway. Ann N Y Acad Sci. 2004 Dec;1030:28-36.

We demonstrate that exogenous, recombinant, TIMP-1 efficiently prevents apoptosis induced by TNFalpha in cycloheximide-sensitized ECs.
4(0,0,0,4) Details
15707762 Anandharajan R, Pathmanathan K, Shankernarayanan NP, Vishwakarma RA, Balakrishnan A: Upregulation of Glut-4 and PPAR gamma by an isoflavone from Pterocarpus marsupium on L6 myotubes: a possible mechanism of action. J Ethnopharmacol. 2005 Feb 28;97(2):253-60. Epub 2005 Jan 13.

The purpose of the present study is to analyse the influence of Pterocarpus marsupium methanolic extract and isolated Pterocarpus marsupium isoflavone on a battery of cellular targets Glut-4, PPAR gamma and PI3 kinase.
The inhibitory effect of cycloheximide on Pterocarpus marsupium methanolic extract and Pterocarpus marsupium isoflavone-mediated glucose uptake suggested that new protein synthesis is required for elevated Glut-4 protein expression.
2(0,0,0,2) Details
17209135 Kuang PP, Zhang XH, Rich CB, Foster JA, Subramanian M, Goldstein RH: Activation of elastin transcription by transforming growth factor-beta in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2007 Apr;292(4):L944-52. Epub 2007 Jan 5.

The induction of elastin hnRNA and mRNA expression by TGF-beta was abolished by pretreatments with TGF-beta receptor I inhibitor, global transcription inhibitor actinomycin D, and partially blocked by addition of protein synthesis inhibitor cycloheximide, but was not affected by the p44/42 MAPK inhibitor U0126.
Inhibition of phosphatidylinositol 3-kinase and Akt phosphorylation by LY-294002 abolished TGF-beta-induced increases in elastin hnRNA and mRNA expression.
2(0,0,0,2) Details
19070612 Cazarolli LH, Folador P, Moresco HH, Brighente IM, Pizzolatti MG, Silva FR: Mechanism of action of the stimulatory effect of apigenin-6-C-(2''-O-alpha-l-rhamnopyranosyl)-beta-L-fucopyranoside on 14C-glucose uptake. Chem Biol Interact. 2009 May 15;179(2-3):407-12. Epub 2008 Nov 25.

The effect of compound 1 on glucose uptake was completely nullified by wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), RO318220, an inhibitor of protein kinase C (PKC), PD98059, a specific inhibitor of mitogen-activated protein kinase (MEK), cycloheximide, an inhibitor of protein synthesis, and colchicine, a microtubule-depolymerizing agent.
The effect of compound 1 on glucose uptake was completely nullified by wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), RO318220, an inhibitor of protein kinase C (PKC), PD98059, a specific inhibitor of mitogen-activated protein kinase (MEK), cycloheximide, an inhibitor of protein synthesis, and colchicine, a microtubule-depolymerizing agent.
1(0,0,0,1) Details
15788394 Hansen IA, Attardo GM, Roy SG, Raikhel AS: Target of rapamycin-dependent activation of S6 kinase is a central step in the transduction of nutritional signals during egg development in a mosquito. J Biol Chem. 2005 May 27;280(21):20565-72. Epub 2005 Mar 23.


This increase is sensitive to the TOR inhibitor rapamycin in a concentration-dependent manner but not to the phosphatidylinositol 3-kinase/phosphatidylinositol 3-kinase-related kinase inhibitor LY294002, the MAPK inhibitor PD98059, or the translational inhibitor cycloheximide.
0(0,0,0,0) Details
18234961 Chetoui N, Sylla K, Gagnon-Houde JV, Alcaide-Loridan C, Charron D, Al-Daccak R, Aoudjit F: Down-regulation of mcl-1 by small interfering RNA sensitizes resistant melanoma cells to fas-mediated apoptosis. Mol Cancer Res. 2008 Jan;6(1):42-52.


In this study, we report that treatment of Fas-resistant melanoma cell lines with cycloheximide, a general inhibitor of de novo protein synthesis, sensitizes them to anti-Fas monoclonal antibody (mAb)-induced apoptosis.
0(0,0,0,0) Details
16716914 Anandharajan R, Jaiganesh S, Shankernarayanan NP, Viswakarma RA, Balakrishnan A: In vitro glucose uptake activity of Aegles marmelos and Syzygium cumini by activation of Glut-4, PI3 kinase and PPARgamma in L6 myotubes. Phytomedicine. 2006 Jun;13(6):434-41. Epub 2005 Nov 2.

The inhibitory effect of cycloheximide on A. marmelos- and S. cumini-mediated glucose uptake suggested that new protein synthesis is required for the elevated glucose transport.
4(0,0,0,4) Details
16912191 Ma Y, Yu WD, Kong RX, Trump DL, Johnson CS: Role of nongenomic activation of phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase 1/2 pathways in 1,25D3-mediated apoptosis in squamous cell carcinoma cells. Cancer Res. 2006 Aug 15;66(16):8131-8.

These effects were nongenomic: they occurred rapidly and were not inhibited by cycloheximide or actinomycin D.
3(0,0,0,3) Details
15946238 Zhu MJ, Kim CD, Kwon YB, Kye KC, Chen YY, Lee WH, Lee S, Lim JS, Seo YJ, Suhr KB, Park JK, Lee JH: Induction of connective tissue growth factor expression by sphingosylphosphorylcholine in cultured human skin fibroblasts. Exp Dermatol. 2005 Jul;14(7):509-14.


Pretreatment with cycloheximide did not prevent the CTGF induction by SPC, indicating that SPC stimulates CTGF mRNA expression without the increased synthesis of a regulatory protein.
0(0,0,0,0) Details
19339694 Salogni L, Musso T, Bosisio D, Mirolo M, Jala VR, Haribabu B, Locati M, Sozzani S: Activin A induces dendritic cell migration through the polarized release of CXC chemokine ligands 12 and 14. Blood. 2009 Jun 4;113(23):5848-56. Epub 2009 Apr 1.


Conversely, activin A was not active on plasmacytoid dendritic cells (DCs) or mature myeloid DCs. iDC migration to activin A was phosphatidylinositol 3-kinase gamma-dependent, Bordetella pertussis toxin- and cycloheximide-sensitive, and was inhibited by M3, a viral-encoded chemokine-binding protein.
0(0,0,0,0) Details
16704410 Harrison EM, McNally SJ, Devey L, Garden OJ, Ross JA, Wigmore SJ: Insulin induces heme oxygenase-1 through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in renal cells. FEBS J. 2006 Jun;273(11):2345-56.

The induction of heme oxygenase-1 in renal adenocarcinoma cells was blocked by actinomycin D and cycloheximide and was abolished by the phosphatidylinositol 3-kinase inhibitor, LY294002, but not by the inactive analog LY303511.
3(0,0,0,3) Details
16506055 Doronzo G, Russo I, Mattiello L, Riganti C, Anfossi G, Trovati M: Insulin activates hypoxia-inducible factor-1alpha in human and rat vascular smooth muscle cells via phosphatidylinositol-3 kinase and mitogen-activated protein kinase pathways: impairment in insulin resistance owing to defects in insulin signalling. Diabetologia. 2006 May;49(5):1049-63. Epub 2006 Feb 28.

The insulin-induced increase of HIF-1alpha is blunted by the translation inhibitor cycloheximide, LY294002, PD98059, SP600125 and rapamycin, but not by SB203580.
2(0,0,0,2) Details
16480751 Wu CC, Hsieh CW, Lai PH, Lin JB, Liu YC, Wung BS: Upregulation of endothelial heme oxygenase-1 expression through the activation of the JNK pathway by sublethal concentrations of acrolein. Toxicol Appl Pharmacol. 2006 Aug 1;214(3):244-52. Epub 2006 Feb 15.


Moreover, acrolein-mediated HO-1 induction is abrogated in the presence of actinomycin D and cycloheximide.
0(0,0,0,0) Details
15735708 Rodrigue CM, Porteu F, Navarro N, Bruyneel E, Bracke M, Romeo PH, Gespach C, Garel MC: The cancer chemopreventive agent resveratrol induces tensin, a cell-matrix adhesion protein with signaling and antitumor activities. Oncogene. 2005 May 5;24(20):3274-84.


Tensin, a cell-matrix adhesion protein binding the integrins and cytoskeletal actin filaments also interacts with PI3-kinase and JNK signaling pathways.
2(0,0,0,2) Details
16378625 Wu CC, Hsu MC, Hsieh CW, Lin JB, Lai PH, Wung BS: Upregulation of heme oxygenase-1 by Epigallocatechin-3-gallate via the phosphatidylinositol 3-kinase/Akt and ERK pathways. Life Sci. 2006 May 15;78(25):2889-97. Epub 2005 Dec 27.

Furthermore, EGCG-mediated HO-1 induction was abrogated in the presence of actinomycin D and cycloheximide, indicating that this upregulation of HO-1 occurred at the transcriptional level.
2(0,0,0,2) Details
19661440 Li JH, D'Alessio A, Pober JS: Lipopolysaccharide can trigger a cathepsin B-dependent programmed death response in human endothelial cells. Am J Pathol. 2009 Sep;175(3):1124-35. Epub 2009 Aug 6.

In the presence of the protein synthesis inhibitor cycloheximide, LPS primarily induces caspase-dependent apoptotic cell death of HUVECs, which is blocked by siRNA-mediated knockdown of myeloid differentiation factor 88 adaptor protein but not of Toll-like receptor-associated interferon-inducing factor.
Finally, in the presence of either the phosphatidylinositol 3 kinase inhibitor LY294002 or the inflammatory cytokine interferon-gamma, LPS activates both caspase- and Cat B-dependent death pathways.
2(0,0,0,2) Details
18565131 Arayatrakoollikit U, Pavasant P, Yongchaitrakul T: Thrombin induces osteoprotegerin synthesis via phosphatidylinositol 3'-kinase/mammalian target of rapamycin pathway in human periodontal ligament cells. J Periodontal Res. 2008 Oct;43(5):537-43. Epub 2008 Jun 28.

The inductive effect was inhibited by cycloheximide, but not by indomethacin.
2(0,0,0,2) Details
17885094 Canas N, Valero T, Villarroya M, Montell E, Verges J, Garcia AG, Lopez MG: Chondroitin sulfate protects SH-SY5Y cells from oxidative stress by inducing heme oxygenase-1 via phosphatidylinositol 3-kinase/Akt. J Pharmacol Exp Ther. 2007 Dec;323(3):946-53. Epub 2007 Sep 20.

The protective effects of CS were prevented by chelerythrine, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), cycloheximide, and Sn (IV)-protoporphyrin IX.
2(0,0,0,2) Details
20229525 Lei YP, Liu CT, Sheen LY, Chen HW, Lii CK: Diallyl disulfide and diallyl trisulfide protect endothelial nitric oxide synthase against damage by oxidized low-density lipoprotein. Mol Nutr Food Res. 2010 Mar 12.

This protection can be attributed partly to their mediation of phosphatidylinositol 3-kinase/protein kinase B signaling and prevention of eNOS degradation.
When cycloheximide was added to block protein synthesis, DADS and DATS suppressed eNOS protein degradation similarly to that noted by MG132.
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