Small molecule schweinfurthins selectively inhibit cancer cell proliferation and mTOR/AKT signaling by interfering with trans-Golgi-network trafficking

References

• Hung DT, Jamison TF, Schreiber SL. Understanding and controlling the cell cycle with natural products. Chem Biol 1996; 3:623–39; PMID:8807895; http://dx.doi.org/10.1016/S1074-5521(96)90129-5
   PubMed Web of Science ®Google Scholar
• Beutler JA, Shoemaker RH, Johnson T, Boyd MR. Cytotoxic geranyl stilbenes from Macaranga schweinfurthii. J Nat Prod 1998; 61:1509–12; PMID:9868152; http://dx.doi.org/10.1021/np980208m
   PubMed Web of Science ®Google Scholar
• Yoder BJ, Cao S, Norris A, Miller JS, Ratovoson F, Razafitsalama, J, Andriantsiferana, R, Rasamison, VE, Kingston, DGl. Antiproliferative prenylated stilbenes and flavonoids from Macaranga alnifolia from the Madagascar rainforest. J Nat Prod 2007; 70:342–6; PMID:17326683; http://dx.doi.org/10.1021/np060484y
   PubMed Web of Science ®Google Scholar
• Neighbors JD, Salnikova MS, Beutler JA, Wiemer DF. Synthesis and structure-activity studies of schweinfurthin B analogs: Evidence for the importance of a D-ring hydrogen bond donor in expression of differential cytotoxicity. Bioorg Med Chem 2006; 14:1771–84; PMID:16290161; http://dx.doi.org/10.1016/j.bmc.2005.10.025
   PubMed Web of Science ®Google Scholar
• Turbyville TJ, Gürsel DB, Tuskan RG, Walrath JC, Lipschultz CA, Lockett SJ, Wiemer DF, Beutler JA, Reilly KM. Schweinfurthin A selectively inhibits proliferation and Rho signaling in glioma and neurofibromatosis type 1 tumor cells in a NF1-GRD-dependent manner. Mol Cancer Ther 2010; 9:1234–43; PMID:20442305; http://dx.doi.org/10.1158/1535-7163.MCT-09-0834
   PubMed Web of Science ®Google Scholar
• Kodet JG, Wiemer DF. Synthesis of indole analogues of the natural schweinfurthins. J Org Chem 2013; 78:9291–302; PMID:24004185; http://dx.doi.org/10.1021/jo4014244
   PubMed Web of Science ®Google Scholar
• Kuder CH, Sheehy RM, Neighbors JD, Wiemer DF, Hohl RJ. Functional evaluation of a fluorescent schweinfurthin:mechanism of cytotoxicity and intracellular quantification. Mol Pharmacol 2012; 82:9–16; PMID:22461663; http://dx.doi.org/10.1124/mol.111.077107
   PubMed Web of Science ®Google Scholar
• Burgett AW, Poulsen TB, Wangkanont K, Anderson DR, Kikuchi C, Shimada K, Okubo S, Fortner KC, Mimaki Y, Kuroda M, et al. Natural products reveal cancer cell dependence on oxysterol-binding proteins. Nat Chem Biol, 2011; 7:639–47; PMID:21822274; http://dx.doi.org/10.1038/nchembio.625
   PubMed Web of Science ®Google Scholar
• Raychaudhuri S, Prinz WA. The diverse functions of oxysterol-binding proteins. Annu Rev Cell Dev Biol 2010; 26:157–77; PMID:19575662; http://dx.doi.org/10.1146/annurev.cellbio.042308.113334
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144:646–74; PMID:21376230; http://dx.doi.org/10.1016/j.cell.2011.02.013
   PubMed Web of Science ®Google Scholar
• Huse JT, Holland EC. Targeting brain cancer: advances in the molecular pathology of malignant glioma. Nat Rev Cancer 2010; 10:319–31; PMID:20414201; http://dx.doi.org/10.1038/nrc2818
   PubMed Web of Science ®Google Scholar
• Hoeller D, Volarevic S, Dikic I. Compartmentalization of growth factor receptor signalling. Curr Opin Cell Biol 2005; 17:107–11; PMID:15780584; http://dx.doi.org/10.1016/j.ceb.2005.01.001
   PubMed Web of Science ®Google Scholar
• Gonnord P, Blouin CM, Lamaze C. Membrane trafficking and signaling: two sides of the same coin. Semin Cell Dev Biol 2011; 23:154–64; PMID:22085846; http://dx.doi.org/10.1016/j.semcdb.2011.11.002
   PubMed Web of Science ®Google Scholar
• Pfeffer SR. Rab GTPase regulation of membrane identity. Curr Opin Cell Biol 2013:25:414–9; PMID:23639309; http://dx.doi.org/10.1016/j.ceb.2013.04.002
   PubMed Web of Science ®Google Scholar
• Nagy P, Vereb G, Sebestyén Z, Horváth G, Lockett SJ, Damjanovich S, Park JW, Jovin TM, Szollosi J. Lipid rafts and the local density of ErbB proteins influence the biological role of homo-and heteroassociations of ErbB2. J Cell Sci 2002; 115:4251–62; PMID:12376557; http://dx.doi.org/10.1242/jcs.00118
   PubMed Web of Science ®Google Scholar
• Huo H, Guo X, Hong S, Jiang M, Liu X, Liao K. Lipid rafts/caveolae are essential for insulin-like growth factor-1 receptor signaling during 3T3-L1 preadipocyte differentiation induction. J Biol Chem 2003; 278:11561–9; PMID:12538586; http://dx.doi.org/10.1074/jbc.M211785200
   PubMed Web of Science ®Google Scholar
• Santiago-Tirado FH, Bretscher A. Membrane-trafficking sorting hubs: cooperation between PI4P and small GTPases at the trans-Golgi network. Trends Cell Biol 2011; 21:515–25; PMID:21764313; http://dx.doi.org/10.1016/j.tcb.2011.05.005
   PubMed Web of Science ®Google Scholar
• Cheung LW, Hennessy BT, Li J, Yu S, Myers AP, Djordjevic B, Lu Y, Stemki-Hale K, Dyer MD, Zhang F, et al. High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stability. Cancer Discov 2011; 1:170–85; PMID:21984976; http://dx.doi.org/10.1158/2159-8290.CD-11-0039
   PubMed Web of Science ®Google Scholar
• James MF, Han S, Polizzano C, Plotkin SR, Manning BD, Stemmer-Rachamimov AO, Gusella JF, Ramesh V. NF2/merlin is a novel negative regulator of mTOR complex 1, and activation of mTORC1 is associated with meningioma and schwannoma growth. Mol Cell Biol 2009; 29:4250–4261; PMID:19451225; http://dx.doi.org/10.1128/MCB.01581-08
   PubMed Web of Science ®Google Scholar
• Maira SM, Stauffer F, Brueggen J, Furet P, Schnell C, Fritsch C, Brachmann S, Chene P, De Pover A, Schoemaker K, et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther 2008; 7:1851–63; PMID:18606717; http://dx.doi.org/10.1158/1535-7163.MCT-08-0017
   PubMed Web of Science ®Google Scholar
• Smith DF, Song X, Cummings RD. Use of glycan microarrays to explore specificity of glycan-binding proteins. Methods Enzymol 2010; 480:417–44; PMID:20816220; http://dx.doi.org/10.1016/S0076-6879(10)80033-3
   PubMed Web of Science ®Google Scholar
• Bao X, Kobayashi M, Hatakeyama S, Angata K, Gullberg D, Nakayama J, Fukuda MN, Fukuda M. Tumor suppressor function of laminin-binding alpha-dystroglycan requires a distinct beta3-N-acetylglucosaminyltransferase. PNAS USA 2009; 106:12109–14; PMID:19587235; http://dx.doi.org/10.1073/pnas.0904515106
   PubMed Web of Science ®Google Scholar
• El-Battari A, Prorok M, Angata K, Mathieu S, Zerfaoui M, Ong E, Suzuki M, Lombardo D, Fukuda M. Different glycosyltransferases are differentially processed for secretion, dimerization, and autoglycosylation. Glycobiology 2003; 13:941–53; PMID:14514709; http://dx.doi.org/10.1093/glycob/cwg117
   PubMed Web of Science ®Google Scholar
• Topczewski JJ, Kuder CH, Neighbors JD, Hohl RJ, Wiemer DF. Fluorescent schweinfurthin B and F analogs with anti-proliferative activity. Bioorg Med Chem 2010; 18:6734–41; PMID:20724169; http://dx.doi.org/10.1016/j.bmc.2010.07.056
   PubMed Web of Science ®Google Scholar
• Burd CG. Physiology and pathology of endosome-to-Golgi retrograde sorting. Traffic 2011; 12:956–62; PMID:21463456; http://dx.doi.org/10.1111/j.1600-0854.2011.01188.x
   PubMed Web of Science ®Google Scholar
• Hill MM, Feng J, Hemmings BA. Identification of a plasma membrane Raft-associated PKB Ser473 kinase activity that is distinct from ILK and PDK1. Curr Biol 2002; 12:1251–5; PMID:12176337; http://dx.doi.org/10.1016/S0960-9822(02)00973-9
   PubMed Web of Science ®Google Scholar
• Holstein SA, Kuder CH, Tong H, Hohl RJ. Pleiotropic effects of a schweinfurthin on isoprenoid homeostasis. Lipids 2011; 46:907–21; PMID:21633866; http://dx.doi.org/10.1007/s11745-011-3572-y
   PubMed Web of Science ®Google Scholar
• Isotani S, Hara K, Tokunaga C, Inoue H, Avruch J, Yonezawa K. Immunopurified mammalian target of rapamycin phosphorylates and activates p70 S6 kinase alpha in vitro. J Biol Chem, 1999; 274:344933–8; PMID:10567431; http://dx.doi.org/10.1074/jbc.274.48.34493
   PubMed Web of Science ®Google Scholar
• Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L, Sabatini DM. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 2008; 320:1496–501; PMID:18497260; http://dx.doi.org/10.1126/science.1157535
   PubMed Web of Science ®Google Scholar
• Kim I, Xu W, Reed JC. Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat Rev Drug Disc 2008; 7:1013–30; PMID:19043451; http://dx.doi.org/10.1038/nrd2755
   PubMed Web of Science ®Google Scholar
• Yung HW, Charnock-Jones DS, Burton GJ. Regulation of AKT phosphorylation at Ser473 and Thr308 by endoplasmic reticulum stress modulates substrate specificity in a severity dependent manner. PloS One 2011; 6:e17894; PMID:21445305; http://dx.doi.org/10.1371/journal.pone.0017894
   PubMed Web of Science ®Google Scholar
• Küppers R. Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer 2005; 5:251–62; PMID:15803153; http://dx.doi.org/10.1038/nrc1589
   PubMed Web of Science ®Google Scholar
• Kloo B, Nagel D, Pfeifer M, Grau M, Düwel M, Vincendeau M, Dorken B, Lenz P, Lenz G, Krappmann D. Critical role of PI3K signaling for NF-kappaB-dependent survival in a subset of activated B-cell-like diffuse large B-cell lymphoma cells. PNAS USA 2011; 108:272–7; PMID:21173233; http://dx.doi.org/10.1073/pnas.1008969108
   PubMed Web of Science ®Google Scholar
• Pfeifer M, Grau M, Lenze D, Wenzel SS, Wolf A, Wollert-Wulf B, Dietze K, Nogai H, Storek B, Madle H, et al. PTEN loss defines a PI3K/AKT pathway-dependent germinal center subtype of diffuse large B-cell lymphoma. PNAS USA 2013; 110:12420–5; PMID:23840064; http://dx.doi.org/10.1073/pnas.1305656110
   PubMed Web of Science ®Google Scholar
• Du X, Kumar J, Ferguson C, Schulz TA, Ong YS, Hong W, Prinz WA, Parton RG, Brown AJ, Yang H. A role for oxysterol-binding protein-related protein 5 in endosomal cholesterol trafficking. J Cell Biol 2011; 192:121–35; PMID:21220512; http://dx.doi.org/10.1083/jcb.201004142
   PubMed Web of Science ®Google Scholar
• Raychaudhuri S, Im YJ, Hurley JH, Prinz WA. Nonvesicular sterol movement from plasma membrane to ER requires oxysterol-binding protein-related proteins and phosphoinositides. J Cell Biol 2006; 173:107–19; PMID:16585271; http://dx.doi.org/10.1083/jcb.200510084
   PubMed Web of Science ®Google Scholar
• Wood CS, Schmitz KR, Bessman NJ, Setty TG, Ferguson KM, Burd CG. PtdIns4P recognition by Vps74/GOLPH3 links PtdIns 4-kinase signaling to retrograde Golgi trafficking. J Cell Biol 2009; 187:967–75; PMID:20026658; http://dx.doi.org/10.1083/jcb.200909063
   PubMed Web of Science ®Google Scholar
• Scott KL, Kabbarah O, Liang MC, Ivanova E, Anagnostou V, Wu J, Dhakal S, Wu M, Chen S, Feinberg, T, et al. GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer. Nature 2009; 459:1085–90; PMID:19553991; http://dx.doi.org/10.1038/nature08109
   PubMed Web of Science ®Google Scholar
• Kobuna H, Inoue T, Shibata M, Gengyo-Ando K, Yamamoto A, Mitani S, Arai H. Multivesicular body formation requires OSBP-related proteins and cholesterol. PLoS Genet 2010; 6. Pii:e1001055; PMID:20700434; http://dx.doi.org/10.1371/journal.pgen.1001055
   PubMedGoogle Scholar
• Mousley CJ, Yuan P, Gaur NA, Trettin KD, Nile AH, Deminoff SJ, Dewar BJ, Wolpert M, Macdonald JM, Herman PK. A sterol-binding protein integrates endosomal lipid metabolism with TOR signaling and nitrogen sensing. Cell 2012; 148:702–15; PMID:22341443; http://dx.doi.org/10.1016/j.cell.2011.12.026
   PubMed Web of Science ®Google Scholar
• Morad SA, Cabot MC. Ceramide-orchestrated signaling in cancer cells. Nat Rev Cancer 2013; 13:51–65; PMID:23235911; http://dx.doi.org/10.1038/nrc3398
   PubMed Web of Science ®Google Scholar
• Ogretmen B, Hannun YA. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer 2004; 4:604–16; PMID:15286740; http://dx.doi.org/10.1038/nrc1411
   PubMed Web of Science ®Google Scholar
• Ohtsubo K, Marth JD. Glycosylation in cellular mechanisms of health and disease. Cell 2006; 126:855–67; PMID:16959566; http://dx.doi.org/10.1016/j.cell.2006.08.019
   PubMed Web of Science ®Google Scholar
• Xu Q, Huang KC, Tendyke K, Marsh J, Liu J, Qiu D, Littlefield BA, Nomoto K, Atasoylu O, Risatti CA, Sperry JB, Smith AB 3rd. In vitro and in vivo anticancer activity of (+)-spongistatin 1. Anticancer Res 2011; 31:2773–9; PMID:21868519
   PubMed Web of Science ®Google Scholar
• R Development Core Team. R: A Language and Environment for Statistical Computing. 2010; Vienna, Austria: R Foundation for Statistical Computing.
   Google Scholar