Supplementary Table 1: Comparison of expression changes of selected measured by microarray analysis and quantitative real-time PCR assay.

Name GenBank SFN DBM SFN + DBM Tumor NM Tumor NM Tumor NM Ugt2b5 NM_009467 Microarray 2.37 2.75 12.17 25.30 9.83 13.10 Real-time 1.95 3.60 10.31 31.62 7.77 18.93 Gstm1 J03952 Microarray 2.19 2.13 13.34 19.74 8.53 13.65 Real-time 1.28 3.12 37.33 174.37 19.76 67.83 Gclc BC019374 Microarray - 2.42 7.17 19.30 6.03 11.23 Real-time - 2.25 8.42 37.62 6.92 17.96 Clu BB433678 Microarray - - - 0.26 - 0.27 Real-time - - - 0.17 - 0.23 Gstm3 J03953 Microarray 2.17 3.57 12.88 18.96 10.74 13.45 Real-time 1.98 4.42 15.72 28.74 11.31 18.53 Clu AV075715 Microarray - - - 0.27 - 0.27 Real-time - - - 0.15 - 0.32 Ephx1 NM_010145 Microarray - 2.77 7.10 20.95 5.00 9.25 Real-time - 3.21 8.23 25.06 6.03 11.09 Ltb4dh BC014865 Microarray - - 2.62 - 2.36 4.64 Real-time - - 3.49 - 2.61 8.06 Cbr3 AK003232 Microarray 2.90 7.16 32.92 95.19 25.71 46.24 Real-time 4.24 6.24 33.78 223.10 16.16 92.34

1 Supplementary Table 2: profiles of SFN, DBM and combinatorial treatment in intestinal tumor and normal-appearing mucosa of ApcMin/+ mice.

Gene Description Name GenBank SFNa DBMa SFN + DBMa

Tumor NM Tumor NM Tumor NM Heat shock heat shock protein 1A Hspa1a M12573 2.12 heat shock factor 2 Hsf2 BC018414 11.86

Ubiquitination and proteolysis carboxyl ester lipase Cel BC006872 109.38 elastase 3B, pancreatic Ela3b NM_026419 412.92 4.64 elastase 3B, pancreatic Ela3b BI439657 385.51 4.00 matrix metalloproteinase 8 Mmp8 NM_008611 0.34 matrix metalloproteinase 9 Mmp9 NM_013599 0.47 matrix metalloproteinase 15 Mmp15 NM_008609 0.18 0.49 matrix metalloproteinase 14 Mmp14 BB535404 0.34 2.32 (membrane-inserted) matrix metalloproteinase 14 Mmp14 NM_008608 0.46 (membrane-inserted) matrix metalloproteinase 19 Mmp19 AF153199 0.13 matrix metalloproteinase 24 Mmp24 BB335489 0.08 2.30 0.12

Electron transport arachidonate 12-lipoxygenase Alox12 BB554189 0.35 carbonyl reductase 1 Cbr1 NM_007620 2.90 3.95 2.95 2.92 carbonyl reductase 3 Cbr3 AK003232 2.90 7.16 32.92 95.19 25.71 46.24 catalase Cat NM_009804 2.50 2.03 cytochrome P450, family 1, Cyp1a1 NM_009992 2.39 3.63 2.24 subfamily a, polypeptide 1 cytochrome P450, family 2, Cyp2a4 NM_007812 0.14 2.67 31.45 448.69 18.87 52.56 subfamily a, polypeptide 4 cytochrome P450, family 2, Cyp2b9 NM_010000 2.86 2.41 subfamily b, polypeptide 9 cytochrome P450, family 2, Cyp2b20 AF128849 6.00 8.38 6.61 6.56 subfamily b, polypeptide 20 cytochrome P450, family 2, Cyp2c29 NM_007815 48.36 93.71 34.38 45.14 subfamily c, polypeptide 29 cytochrome P450, family 2, Cyp2d10 BC010989 0.36 0.48 0.43 subfamily d, polypeptide 10 cytochrome P450, family 2, Cyp2e1 NM_021282 0.27 0.31 subfamily e, polypeptide 1 contactin 1 Cntn1 NM_007727 0.28 cytochrome P450, family 2, Cyp2j9 AF336850 0.15 0.24 subfamily j, polypeptide 9 cytochrome P450, family 3, Cyp3a25 AF204959 2.43 subfamily a, polypeptide 25 epoxide 1, microsomal Ephx1 NM_010145 2.77 7.10 20.95 5.00 9.25 2, cytoplasmic Ephx2 NM_007940 2.32 leukotriene B4 12- Ltb4dh BC014865 2.62 2.36 4.64 hydroxydehydrogenase superoxide dismutase 2, Sod2 NM_013671 2.21 2.35 mitochondrial

Detoxification glutamate-cysteine , catalytic Gclc BC019374 2.42 7.17 19.30 6.03 11.23 subunit glutamate-cysteine ligase, catalytic Gclc AW825835 6.32 13.22 5.47 8.07 subunit glutamate-cysteine ligase , modifier Gclm NM_008129 2.59 6.46 2.26 3.75 subunit glutathione S-, alpha 2 Gsta2 NM_008182 2.38 4.62 2.68 2.44 2.72 2.29 (Yc2)

2 Gene Description Name GenBank SFNa DBMa SFN + DBMa

Tumor NM Tumor NM Tumor NM glutathione S-transferase, alpha 3 Gsta3 AI172943 2.44 3.14 7.95 2.96 3.75 glutathione S-transferase, alpha 4 Gsta4 NM_010357 5.21 3.30 3.50 glutathione S-transferase, mu 1 Gstm1 J03952 2.36 2.13 11.58 15.58 7.74 9.79 glutathione S-transferase, mu 1 Gstm1 NM_010358 3.28 18.41 29.85 16.90 24.81 glutathione S-transferase, mu 2 Gstm2 NM_008183 8.72 2.45 3.42 glutathione S-transferase, mu 3 Gstm3 J03953 2.17 3.20 9.74 6.55 8.53 6.69 glutathione S-transferase, mu 4 Gstm4 AF464943 5.17 18.12 3.97 7.64 glutathione synthetase Gss NM_008180 3.25 2.04 glutathione reductase 1 Gsr AK019177 4.12 2.44 glutathione peroxidase 5 Gpx5 NM_010343 0.19 0.27 glutathione peroxidase 6 Gpx6 AV001252 0.13 glutathione peroxidase 7 Gpx7 NM_024198 0.48 0.44 heme oxygenase (decycling) 1 Hmox1 NM_010442 5.40 0.43 5.37 8.64 metallothionein 1 Mt1 NM_013602 2.16 4.30 metallothionein 2 Mt2 AA796766 6.43 thioredoxin reductase 1 Txnrd1 BB284199 2.89 thioredoxin reductase 1 Txnrd1 AV377065 2.52 2.21 thioredoxin reductase 2 Txnrd2 NM_013711 2.33 thioredoxin reductase 2 Txnrd2 BE948556 2.03 thioredoxin reductase 3 Txnrd3 AF349659 11.25 4.38 7.38 UDP-glucuronosyltransferase 2 Ugt2b5 NM_009467 2.37 2.75 12.17 25.30 9.83 13.10 family, member 5

Transporter apolipoprotein D Apod NM_007470 0.43 ATP-binding cassette, sub-family B Abcb1a M30697 2.90 (MDR/TAP), member 1A ATP-binding cassette, sub-family C Abcc2 NM_013806 7.19 4.04 (CFTR/MRP), member 2 ATP-binding cassette, sub-family C Abcc3 AK006128 5.51 2.95 2.65 (CFTR/MRP), member 3 ATP-binding cassette, sub-family Abcg4 BC026477 0.43 G (WHITE), member 4 ATP-binding cassette, sub-family Abcg3 NM_030239 0.42 G (WHITE), member 3 fatty acid binding protein 3, muscle Fabp3 NM_010174 0.45 and heart

Cell apoptosis and growth control Bcl2-like 10 Bcl2l10 NM_013479 5.06 2.10 3.98 BRCA1 associated protein Brap NM_028227 0.48 2.98 2.17 breast carcinoma amplified Bcas3 BG069872 0.41 0.32 sequence 3 breast carcinoma amplified Bcas3 AK011603 2.09 2.13 sequence 3 breast cancer 1 Brca1 BC003248 0.46 clusterin Clu NM_013492 0.32 0.25 clusterin Clu AV075715 0.27 0.27 clusterin Clu BB433678 0.26 0.27 clusterin Clu AV152288 0.23 0.20 cyclin E2 Ccne2 BB224305 0.10 2.29 cyclin M2 Cnnm2 BB278418 0.42 0.37 cyclin T2 Ccnt2 BI872151 0.48 EGF-like-domain, multiple 4 Egfl4 BE573060 0.49 EGF-like-domain, multiple 6 Egfl6 NM_019397 0.17 0.07 G1 to phase transition 2 Gspt2 BB441361 0.45 3.60 3.76 hepatoma-derived , Hdgfrp3 BB291880 0.49 related protein 3 receptor-related receptor Insrr NM_011832 0.45 insulin-like growth factor 1 Igf1 BG075165 0.42 insulin-like growth factor I receptor Igf1r BE980124 3.36 3.61 insulin-like growth factor I receptor Igf1r BB446952 0.39 insulin-like 5 Insl5 NM_011831 0.48 0.34 insulin promoter factor 1, Ipf1 AK020261 0.42 homeodomain transcription factor

3 Gene Description Name GenBank SFNa DBMa SFN + DBMa

Tumor NM Tumor NM Tumor NM insulin-like growth factor binding Igfbp1 NM_008341 0.38 0.42 0.15 protein 1 insulin-like growth factor binding Igfbp2 AK011784 0.13 protein 2 insulin-like growth factor binding Igfbp5 NM_010518 0.36 0.35 2.11 protein 5 1 family, member 5 NM_019451 0.17 (delta) interleukin 10 Il10 NM_010548 0.43 interleukin 11 Il11 NM_008350 2.29 interleukin 14 Il14 BG070463 0.42 0.48 interleukin 25 Il25 NM_080837 0.39 interleukin 1 receptor-like 1 Il1rl1 D13695 0.46 interleukin 1 receptor-like 1 Il1rl1 NM_010743 0.29 interleukin 1 receptor-like 2 Il1rl2 BG073776 0.40 interleukin-1 receptor-associated Irak3 BB497580 0.42 3 interferon (alpha and beta) receptor Ifnar2 BB522265 0.41 2 phospholipase A2, group IIA Pla2g2a NM_011108 0.47 (, synovial fluid) -derived growth factor, D Pdgfd BB428671 0.35 0.44 0.43 polypeptide platelet derived growth factor Pdgfra BB221015 0.48 receptor, alpha polypeptide prostaglandin I2 (prostacyclin) Ptgis BB324481 0.19 synthase Tnf receptor-associated factor 1 Traf1 BG064103 0.33 Tnf receptor-associated factor 3 Traf3 U21050 0.35 transforming growth factor, beta Tgfbr2 S69114 0.34 receptor II transforming growth factor beta Tbrg4 NM_134011 0.48 regulated gene 4 tumor necrosis factor (ligand) Tnfsf8 NM_009403 0.24 0.37 superfamily, member 8 tumor necrosis factor receptor Tnfrsf12a NM_013749 0.23 0.14 0.16 superfamily, member 12a tumor necrosis factor receptor Tnfrsf19 NM_013869 0.48 superfamily, member 19 tumor necrosis factor receptor Tnfrsf23 NM_024290 0.19 superfamily, member 23 WNT1 inducible signaling pathway Wisp1 NM_018865 0.15 0.26 0.12 0.27 protein 1 wingless-related MMTV Wnt6 AV308073 0.47 integration site 6 wingless-type MMTV integration Wnt9a AB072311 0.24 0.31 0.40 site 9A

Adhesion and chemotaxis cadherin 2 Cdh2 BC022107 2.15 catenin alpha-like 1 Catnal1 BQ031240 0.42 chemokine (C-C motif) ligand 2 Ccl2 AF065933 0.24 chemokine (C-X-C motif) ligand 5 Cxcl5 NM_009141 0.24 chemokine (C-X-C motif) ligand 7 Cxcl7 NM_023785 0.06 chemokine (C-X-C motif) ligand Cxcl13 AF030636 0.49 13 chemokine (C-C) receptor 2 Ccr2 BB148128 0.50 chemokine (C-X-C motif) receptor Cxcr4 D87747 0.48 4 chemokine (C-C motif) receptor 6 Ccr6 NM_009835 0.24 chemokine (C-C motif) receptor 9 Ccr9 NM_009913 0.41

Kinase and phosphatase Eph receptor A3 Epha3 M68513 2.85 0.38 0.49 0.14 Eph receptor A3 Epha3 M68515 16.42 10.52 0.22 6.22 Eph receptor A3 Epha3 AV226618 0.10 0.38 0.34

4 Gene Description Name GenBank SFNa DBMa SFN + DBMa

Tumor NM Tumor NM Tumor NM Eph receptor A4 Epha4 AI385584 6.72 2.50 10.44 Eph receptor A4 Epha4 BB706548 3.26 Eph receptor A4 Epha4 AK013481 0.24 Eph receptor A7 Epha7 BC026153 0.10 0.18 0.39 -coupled receptor kinase 6 Gprk6 AF040749 0.46 activated protein kinase Map2k6 BB540608 0.24 kinase 6 mitogen activated protein kinase Map2k7 NM_011944 2.77 3.53 kinase 7 mitogen activated protein kinase Map3k1 BM240275 0.43 kinase kinase 1 mitogen activated protein kinase Map3k2 NM_011946 0.50 0.20 kinase kinase 2 mitogen-activated protein kinase Map3k6 NM_016693 0.47 kinase kinase 6 mitogen activated protein kinase Map4k1 BB546619 0.16 kinase kinase kinase 1 p21 (CDKN1A)-activated kinase 2 Pak2 AK019899 2.30 p21 (CDKN1A)-activated kinase 3 Pak3 BB468082 0.21 0.18 phosphoinositide-3-kinase adaptor Pik3ap1 BI684288 0.36 protein 1 phosphatidylinositol 3-kinase, Pik3ca BE647269 0.48 catalytic, alpha polypeptide phosphoinositide-3-kinase, Pik3cg BB205102 0.49 catalytic, gamma polypeptide phosphatidylinositol 3-kinase Pik3cd NM_008840 0.31 5.26 5.33 catalytic delta polypeptide phosphatidylinositol 3-kinase, C2 Pik3c2a AA415004 0.47 domain containing, alpha polypeptide , beta Prkcb BF660388 0.41 protein kinase C, gamma Prkcc NM_011102 0.42 protein kinase C, eta Prkch NM_008856 0.13 protein kinase C, zeta Prkcz BB430502 2.09 2.14 RAB, member of RAS oncogene Rabl4 AV205856 0.44 family-like 4 RAB30, member RAS oncogene Rsb30 BG070713 0.40 family Rab38, member of RAS oncogene Rab38 NM_028238 0.46 2.14 family Rab40b, member RAS oncogene Rab40b AV364488 0.18 family Ras-like without CAAX 2 Rit2 BB271919 0.24 0.45 RAS guanyl releasing protein 1 Rasgrp1 BB354696 0.22 Similar to protein kinase C zeta BG143376 0.31 (LOC233024) sphingomyelin phosphodiesterase Smpd2 AK013818 4.97 2.56 7.02 2, neutral sphingomyelin phosphodiesterase Smpd3 NM_021491 0.49 3, neutral sphingosine kinase 1 Sphk1 NM_025367 2.25 src family associated Scap2 BB212597 0.48 phosphoprotein 2

G-protein coupled receptors endothelial differentiation, Edg3 BB532532 0.30 sphingolipid G-protein-coupled receptor, 3 endothelial differentiation, G- Edg6 AV081616 0.48 protein-coupled receptor 6 G protein-coupled receptor 18 Gpr18 BG145550 0.47 G protein-coupled receptor 43 Gpr43 AV370830 0.49 G protein-coupled receptor 49 Gpr49 BB363657 0.44 G protein-coupled receptor 73 Gpr73 BB037474 0.22 0.05 0.19 G protein-coupled receptor 83 Gpr83 AV291031 0.32 G protein-coupled receptor 85 Gpr85 BC026975 0.24

5 Gene Description Name GenBank SFNa DBMa SFN + DBMa

Tumor NM Tumor NM Tumor NM G-protein coupled receptor 88 Gpr88 BE947345 0.41 G protein-coupled receptor 91 Gpr91 NM_032400 0.35 G protein-coupled receptor 120 Gpr120 AV025152 0.43 0.45 prostaglandin F receptor Ptgfr BB559010 0.38 prostaglandin I receptor (IP) Ptgir AV373771 0.31

Transcription factors aryl-hydrocarbon receptor Ahr BE989096 0.42 aryl hydrocarbon receptor nuclear Arntl2 BB713508 0.44 0.10 translocator-like 2 aryl hydrocarbon receptor nuclear Arntl BC011080 0.49 translocator-like cAMP responsive element Crem AU258667 0.11 modulator cAMP responsive element binding Creb1 NM_009952 0.30 protein 1 inhibitor of kappaB kinase gamma Ikbkg BB147462 3.11 inhibitor of kappaB kinase gamma Ikbkg NM_010547 2.68 3.39 inhibitor of kappaB kinase gamma Ikbkg BB821318 2.64 proliferator activated Ppara AI118064 2.09 receptor alpha peroxisome proliferator activated Pparg NM_011146 2.06 receptor gamma peroxisome proliferator activator Ppard AV050195 0.43 3.48 2.44 receptor delta

Lipid Metabolism farnesyl diphosphate farnesyl Fdft1 BB028312 0.49 0.43 transferase 1 lysosomal acid lipase 1 Lip1 AI596237 2.50 phospholipase C, beta 4 Plcb4 BB143801 0.21 phospholipase C, beta 4 Plcb4 BB224034 3.38 0.36 2.39 0.11 phospholipase D2 Pld2 NM_008876 0.26 a The relative mRNA expression levels of each gene in treatment group over vehicle group (fold of change) were listed. Only genes that were upregulated or downregulated more than two folds and with known functions were listed.

6