Nanjoo Suh Assistant Professor Rutgers University Department of Chemical Biology Ernest Mario School of Pharmacy 164 Frelinghuysen Road Piscataway. N.J. 08854-0789 (732) 445-3400. Ext 226 FAX -0687 nsuh@rci.rutgers.edu

Mechanistic study of cancer prevention & inflammation-natural/synthetic agents

Mechanistic study of cancer prevention with natural and synthetic agents such as triterpenoids. rexinoids. deltanoids. and other chemopreventive agents in cancer cell lines as well as in carcinogen-induced animal models; Molecular mechanism studies targeting inflammatory genes such as inducible nitric oxide synthase (iNOS). inducible cyclooxygenase (COX-2). and NF-kB in carcinogenesis.

Selected Publications

Lee HJ, Ji Y, Paul S, Maehr H, Uskokovic M, Suh N. (2007) Activation of bone morphogenetic protein signaling by a Gemini vitamin D3 analogue is mediated by Ras/protein kinase C alpha. Cancer Res. 67(24):11840-7.

Suh N, Paul S, Lee HJ, Ji Y, Lee MJ, Yang CS, Reddy BS, Newmark HL. (2007) Mixed tocopherols inhibit N-methyl-N-nitrosourea-induced mammary tumor growth in rats. Nutr Cancer. ;59(1):76-81.

Koschmieder S, D'Alò F, Radomska H, Schöneich C, Chang JS, Konopleva M, Kobayashi S, Levantini E, Suh N, Di Ruscio A, Voso MT, Watt JC, Santhanam R, Sargin B, Kantarjian H, Andreeff M, Sporn MB, Perrotti D, Berdel WE, Müller-Tidow C, Serve H, Tenen DG. (2007) CDDO induces granulocytic differentiation of myeloid leukemic blasts through translational up-regulation of p42 CCAAT enhancer binding protein alpha. Blood. 110(10):3695-705.

Liby K, Honda T, Williams CR, Risingsong R, Royce DB, Suh N, Dinkova-Kostova AT, Stephenson KK, Talalay P, Sundararajan C, Gribble GW, Sporn MB. (2007) Novel semisynthetic analogues of betulinic acid with diverse cytoprotective, antiproliferative, and proapoptotic activities.
Mol Cancer Ther. 6(7):2113-9.

Maehr H, Uskokovic M, Adorini L, Penna G, Mariani R, Panina P, Passini N, Bono E, Perego S, Biffi M, Holick M, Spina C, Suh N. (2007) Calcitriol derivatives with two different side chains at C-20 III. An epimeric pair of the gemini family with unprecedented antiproliferative effects on tumor cells and renin mRNA expression inhibition. J Steroid Biochem Mol Biol. 103(3-5):277-81.

Suh N, Paul S, Hao X, Simi B, Xiao H, Rimando AM, Reddy BS. (2007) Pterostilbene, an active constituent of blueberries, suppresses aberrant crypt foci formation in the azoxymethane-induced colon carcinogenesis model in rats. Clin Cancer Res. 13(1):350-5.

Liby K, Rendi M, Suh N, Royce DB, Risingsong R, Williams CR, Lamph W, Labrie F, Krajewski S, Xu X, Kim H, Brown P, Sporn MB. (2006) The combination of the rexinoid, LG100268, and a selective estrogen receptor modulator, either arzoxifene or acolbifene, synergizes in the prevention and treatment of mammary tumors in an estrogen receptor-negative model of breast cancer. Clin Cancer Res. 12(19):5902-9.

Banach-Petrosky W, Ouyang X, Gao H, Nader K, Ji Y, Suh N, DiPaola RS, Abate-Shen C. (2006) Vitamin D inhibits the formation of prostatic intraepithelial neoplasia in Nkx3.1;Pten mutant mice. Clin Cancer Res. 12(19):5895-901.

Honda T, Liby KT, Su X, Sundararajan C, Honda Y, Suh N, Risingsong R, Williams CR, Royce DB, Sporn MB, Gribble GW. (2006) Design, synthesis, and anti-inflammatory activity both in vitro and in vivo of new betulinic acid analogues having an enone functionality in ring A.
Bioorg Med Chem Lett. 16(24):6306-9.

Ji Y. Lee HJ. Goodman C. Uskokovic M. Liby K. Sporn M. Suh N. (2006) The synthetic triterpenoid CDDO-imidazolide induces monocytic differentiation by activating the Smad and ERK signaling pathways in HL60 leukemia cells. Mol Cancer Ther. 5(6):1452-1458.

Lee HJ. Liu H. Goodman C. Ji Y. Maehr H. Uskokovic M. Notterman D. Reiss M. Suh N. (2006) Gene expression profiling changes induced by a novel Gemini Vitamin D derivative during the progression of breast cancer. Biochem Pharmacol. May 5; [Epub ahead of print]

Lee HJ. Wislocki A. Goodman C. Ji Y. Ge R. Maehr H. Uskokovic M. Reiss M. Suh N. (2006) A novel vitamin D derivative activates bone morphogenetic protein signaling in MCF10 breast epithelial cells. Mol Pharmacol. 69(6):1840-8.

Hong J. Sang S. Park HJ. Kwon SJ. Suh N. Huang MT. Ho CT. Yang CS. (2006) Modulation of arachidonic acid metabolism and nitric oxide synthesis by garcinol and its derivatives. Carcinogenesis. 27(2):278-86.

Hyer ML. Croxton R. Krajewska M. Krajewski S. Kress CL. Lu M. Suh N. Sporn MB. Cryns VL. Zapata JM. Reed JC. (2005) Synthetic triterpenoids cooperate with tumor necrosis factor-related apoptosis-inducing ligand to induce apoptosis of breast cancer cells. Cancer Res. 65(11):4799-808.

Liby K. Hock T. Yore MM. Suh N. Place AE. Risingsong R. Williams CR. Royce DB. Honda T. Honda Y. Gribble GW. Hill-Kapturczak N. Agarwal A. Sporn MB. (2005) The synthetic triterpenoids. CDDO and CDDO-imidazolide. are potent inducers of heme oxygenase-1 and Nrf2/ARE signaling. Cancer Res. 65(11):4789-98.

Dinkova-Kostova AT. Liby KT. Stephenson KK. Holtzclaw WD. Gao X. Suh N. Williams C. Risingsong R. Honda T. Gribble GW. Sporn MB. Talalay P. (2005) Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress. Proc Natl Acad Sci U S A. 102(12):4584-9.

Rendi MH. Suh N. Lamph WW. Krajewski S. Reed JC. Heyman RA. Berchuck A. Liby K. Risingsong R. Royce DB. Williams CR. Sporn MB. (2004) The selective estrogen receptor modulator arzoxifene and the rexinoid LG100268 cooperate to promote transforming growth factor beta-dependent apoptosis in breast cancer. Cancer Res. 64(10):3566-71.

Dragnev KH. Pitha-Rowe I. Ma Y. Petty WJ. Sekula D. Murphy B. Rendi M. Suh N. Desai NB. Sporn MB. Freemantle SJ. Dmitrovsky E. (2004) Specific chemopreventive agents trigger proteasomal degradation of G1 cyclins: implications for combination therapy. Clin Cancer Res. 10(7):2570-7.

Chauhan D. Li G. Podar K. Hideshima T. Shringarpure R. Catley L. Mitsiades C. Munshi N. Tai YT. Suh N. Gribble GW. Honda T. Schlossman R. Richardson P. Sporn MB. Anderson KC. (2004) The bortezomib/proteasome inhibitor PS-341 and triterpenoid CDDO-Im induce synergistic anti-multiple myeloma (MM) activity and overcome bortezomib resistance. Blood. 103(8):3158-66.

Mix KS. Coon CI. Rosen ED. Suh N. Sporn MB. Brinckerhoff CE. (2004) Peroxisome proliferator-activated receptor-gamma-independent repression of collagenase gene expression by 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and prostaglandin 15-deoxy-delta(12,14) J2: a role for Smad signaling. Mol Pharmacol. 65(2):309-18.

Pedersen IM. Zapata JM. Samuel T. Scott FL. Salvesen GS. Honda T. Gribble GW. Suh N. Sporn MB. Kipps TJ. Reed JC. (2004) Retraction: The triterpenoid CDDO-Imidazolide induces apoptosis and enhances fludarabine-induced apoptosis of CLL B-cells. Blood. 104(4):932.

Honda T. Favaloro FG Jr. Janosik T. Honda Y. Suh N. Sporn MB. Gribble GW. (2003) Efficient synthesis of (-)- and (+)-tricyclic compounds with enone functionalities in rings A and C. A novel class of orally active anti-inflammatory and cancer chemopreventive agents. Org Biomol Chem. 1(24):4384-91.

Suh. N.. Roberts. A.B.. Birkey Reffey S.. Miyazono. K.. Itoh. S.. ten Dijke. P.. Heiss. E.H.. Place. A.E.. Risingsong. R.. Williams. C.R.. Honda. T.. Gribble. G.W.. Sporn. M.B. (2003). Synthetic triterpenoids enhance TGF-b/Smad signaling. Cancer Res. 63:1371-1376.

Place. A. E.. Suh. N.. Williams. C. R.. Risingsong. R.. Honda. T.. Honda. Y.. Gribble. G. W.. Leesnitzer. L. M.. Stimmel. J. B.. Willson. T. M.. Rosen. E.. and Sporn. M. B. (2003). The novel synthetic triterpenoid. CDDO-Imidazolide. inhibits inflammatory response and tumor growth in vivo. Clin. Cancer Res. 9: 2798-2806.

Sporn. M.B.. and Suh. N. (2002). Chemoprevention: an essential approach to controlling cancer. Nature Rev. Cancer 2: 537- 543.

Suh. N.. Lamph. W.W.. Glasebrook. A.L.. Grese. T.A.. Palkowitz. A.D.. Williams. C.R.. Risingsong. R.. Farris. M.R.. Heyman. R.A.. and Sporn. M.B. (2002).Prevention and Treatment of Experimental Breast Cancer with the Combination of a New SERM. Arzoxifene. and a New Rexinoid. LG100268. Clin. Cancer Res. 8: 3270-3275.

Sporn. M.B.. Suh. N.. and Mangelsdorf. D.J. (2001).Prospects for prevention and treatment of cancer with SPARMs (selective PPARg Modulators). Trends Mol. Med. 7:395-400.

Suh. N.. Glasebrook. A.L.. Palkowitz. A.D.. Bryant. H.U.. Burris. L.L.. Starling. J.J.. Pearce. H.L.. Williams. C.. Peer. C.. Wang. Y.. Sporn. M.B. (2001). Arzoxifene. a new selective estrogen receptor modulator for chemoprevention of experimental breast cancer. Cancer Res. 61: 8412-8415.