Table 1.
Compounds that Restore E-cadherin Expression in Genital and Urinary Cancers
| Compound | Description | Cancer | Mechanism and Function | Reference |
|---|---|---|---|---|
| 17-DMCHAG | an Hsp90 inhibitor derived from geldanamycin | PCa | downregulates ZEB1, Snail1, Slug, and vimentin; upregulates E-cadherin; suppresses cell proliferation; induces apoptosis | 33 |
| α-Solanine | a glycoalkaloid in nightshade (Solanum nigrum Linn) | PCa | elevates E-cadherin, RECK, TIMP-1, and TIMP2 levels; reduces vimentin, MMP-2, MMP-9, and EMMPRIN levels; suppresses the phosphorylation of PI3K, Akt, and ERK; inhibits cell viability and invasion; suppresses the EMT | 22 |
| Alisertib | a selective aurora kinase A inhibitor | OC | restores the balance between E-cadherin and N-cadherin; inhibits phosphorylation of Aurora kinase A (AURKA); suppresses Akt/mammalian target of rapamycin (mTOR) and p38 pathways; induces G2/M phase arrest, apoptosis, and autophagy; suppresses the EMT | 57 |
| Antrocin | a sesquiterpene lactone from Antrodia cinnamomea | BCa | promotes the expression of E-cadherin, Fas, DR5, and Bax and activations of caspase-3, -8, and -9; decreases phosphorylation of FAK, paxillin, MMPs, and vimentin; attenuates phosphorylation of ERK and c-Fos; inhibits cell growth, migration, and invasion; induces apoptosis | 45 |
| Berberine | a plant-derived isoquinoline alkaloid | CC | reduces MMP-2, MMP-9, urokinase-type plasminogen activator (uPA), N-cadherin, vimentin, VEGF, and HIF-1α; impedes activation of NF-κB; inhibits cell proliferation, migration, and invasion; enhances apoptosis; reduces tumor growth | 49 |
| BMS-345541 | a highly selective IKK inhibitor | PCa | downregulates N-cadherin, Snail, Slug, and Twist; upregulates E-cadherin and p-NDRG1; inhibits cell proliferation, invasion, and metastasis; induces apoptosis | 26 |
| Caffeic acid (CA) and metformin | metformin, anti-diabetes drug; CA, a natural compound | CC | suppresses the expressions of Snail, MMP-9, vimentin, HIF-1α, and CAIX; enhances the expressions of E-cadherin, occuludin, claudin, and TIMP-1; suppresses the motility of cells; inhibits the EMT process | 50 |
| Carnosol | an analog of resveratrol | OC | restores E-cadherin expression; inhibits cell adhesion, viability, and growth; suppresses EGF-induced EMT | 61 |
| DZ-50 | a lead quinazoline-based Doxazosin derivative | PCa | increases the expression of E-cadherin; decreases the expressions of N-cadherin, talin1, and IGFBP3; inhibits cell invasion; reverses the EMT; impairs tumor growth | 29 |
| Everolimus | an mTOR inhibitor | RCC | reduces p-FAK, p-Src, vimentin, and RhoA levels; increases E-cadherin expression; suppresses lung metastasis | 40 |
| Galeterone, VNPT55 | galeterone, a proprietary compound; VNPT55, a new analog of galeterone | PCa | downregulates Snail, Slug, N-cadherin, vimentin, MMP-2/9, NF-κB, Twist1, β-catenin, CD44, and Nanog; upregulates E-cadherin; inhibits migration and invasion | 37 |
| Ginsenoside Rb1 | an active component of Panax ginseng | OC | upregulates E-cadherin, downregulates vimentin and miR-25, inhibits cell migration, suppresses the EMT | 56 |
| Ginsenoside 20(S)-Rg3 | an active component of Panax ginseng | OC | reduces the expressions of HIF-1α, Snail, and vimentin; upregulates E-cadherin; inhibits EMT | 55 |
| HM015K | a novel silybin derivative | OC | upregulates Bax, Bak, cyclin B1, and E-cadherin; downregulates Bcl-2, N-cadherin, c-Myc, DVL3, DVL2, ABCG2, and ABCB1; induces apoptosis | 59 |
| Honokiol | a natural phenolic compound from Magnolia grandiflora | BCa | induces the expression of E-cadherin; represses the expressions of N-cadherin, SRC-3, MMP-2, and Twist1; suppresses the EMT; inhibits cell migration and invasion | 48 |
| Kallistain | a plasma protein with anti-inflammatory functions | CC | reduces MMP-2, MMP-9, uPA, N-cadherin, vimentin, VEGF, and HIF-1α; impedes activation of NF-κB; inhibits proliferation, migration, and invasion; enhances apoptosis; reduces tumor growth | 51 |
| Litchi seed extract | litchi: known as Chinese cherry, a subtropical fruit tree | PCa | upregulates p21, p27, and E-cadherin; decreases the expressions of vimentin, Snail, cyclin, and CDK; suppresses the Akt/GSK-3β-signaling pathway; inhibits cell migration, invasion, and clonogenic growth; induces apoptosis and cell cycle G1/S phase arrest | 27 |
| Matrine and cisplatin | matrine: a natural compound from the Sophora plant genus | BCa | increases ROS, E-cadherin, β-catenin, Bax, and cleaved caspase-3 levels; decreases fibronectin, vimentin, Bcl-2, p-Akt, p-PI3K, VEGFR2, and VEGF; inhibits migration and invasion; induces cell-cycle arrest; promotes apoptosis | 44 |
| Melatonin | a methoxyindole synthesized and secreted by the pineal gland | OC | decreases the expressions of Ki67, ZEB1, ZEB2, Snail, vimentin, and MMP-9; increases the expression of E-cadherin; inhibits cell proliferation and migration | 62 |
| Metformin | an anti-diabetes drug | PCa | upregulates E-cadherin; downregulates N-cadherin, vimentin, Twist, Snail1, ZEB1, COX2, PGE2, and p-STAT3; inhibits cell migration and invasion; represses the EMT | 24, 25 |
| MLN4924 (pevonedistat) | a suppressor of protein neddylation | RCC | increases the expression of E-cadherin; represses the expressions of vimentin, p21, p27, and Weel; inhibits cell migration and invasion; induces G2/M arrest | 41 |
| MSKE | muscadine grape skin extract | PCa | decreases the levels of superoxide, STAT-3, and vimentin; increases the expression of E-cadherin; reduces cell migration; abrogates the EMT process | 21 |
| N-butylidenephthalide (BP) | derived from Radix Angelica Sinensis (Danggui) | BCa | activates caspase-9 and caspase-3, upregulates E-cadherin, downregulates N-cadherin, increases sensitivity to cisplatin, inhibits cell migration, induces cell death and apoptosis, inhibits tumor growth | 43 |
| NPV-LDE-225 (erimodegib) | a smoothened inhibitor | PCa | promotes the activation of caspase-3 and cleavage of PARP; increases the expressions of Bax, Bak, and E-cadherin; inhibits Bcl-2, Bcl-XL, XIAP, cIAP1, cIAP2, survivin, Gli1, Gli2, Patched-1, Patched-2, Nanog, Oct-4, c-Myc, Sox-2, Bmi-1, N-cadherin, Snail, Slug, and ZEB1; inhibits Shh-signaling pathway; suppresses cell viability and spheroid formation; induces apoptosis; inhibits tumor growth | 20 |
| Osthole | a monomer extract of a traditional Chinese herb | RCC | increases the expressions of cleaved caspase-3, Bax, and E-cadherin; inhibits Bcl-2, survivin, MMP-2, MMP-9, N-cadherin, vimentin, Smad-3, Snail1, and Twist1; suppresses cell proliferation, invasion, migration, and colony formation | 39 |
| PMMB232 | a shikonin coumarin-carboxylic acid | CC | upregulates E-cadherin and PDH-E1α, downregulates HIF-1α and PDK1, inhibits proliferation, induces apoptosis | 52 |
| Resveratrol | a natural polyphenilic agent in grape and red wine | OC | restores E-cadherin expression, downregulates hTERT and HIF-1α, inhibits Src phosphorylation, promotes interference of a Src and HIF-1α/hTERT/Slug-signaling pathway, inhibits cell invasion | 60 |
| Retinamide VNLG-152 | a novel retinamide | PCa | suppresses the expressions of N-cadherin, β-catenin, claudin, Slug, Snail, Twist, vimentin, MMP-2, MMP-9, f-AR/AR-V7, MNK1/2, p-EIF4E, PSA, cyclin D1, and Bcl-2; increases the expression of E-cadherin; inhibits tumor growth and the EMT | 36 |
| Simvastatin | a cholesterol-lowering medication | PCa | reduces N-cadherin and vimentin, increases E-cadherin, inhibits p38 MAPK phosphorylation, suppresses cell migration and invasion, inhibits TGF-β1-induced EMT | 23 |
| Sophra flavescebs alkaloid (SFA) gels | a traditional Chinese medicine | CC | promotes Bax and E-cadherin expressions; suppresses Bcl-2, cyclin A, and MMP-2 levels; inhibits Akt/mTOR-signaling pathway; restrains cell proliferation and metastasis; induces G2/M arrest and apoptosis | 54 |
| Sulforaphane (SFN) | abundant in cruciferous vegetables | PCa | upregulates E-cadherin, downregulates CD44v6 and MMP-2, promotes activation of ERK1/2, inhibits cell invasion and migration | 34 |
| Tanshinone IIA (Tan-IIA) | an extract from Salvia miltiorrhiza | BCa | suppresses MMP-9/-2, N-cadherin, vimentin, Snail, Slug, and CCL2 levels; inhibits phosphorylation of STAT3; upregulates E-cadherin; inhibits cell migration and invasion | 47 |
| Tetramethypyrazine (TMP) | one active element from the Chinese medicinal herb Chuanxiong | RCC | upregulates NKG2D ligands MICA/B and E-cadherin; downregulates vimentin and fibronectin; inhibits cell viability, proliferation, apoptosis, invasion, and migration | 38 |
| Tetrandrine | a bisbenzylisoquinoline alkaloid from Stephaniae | BCa | increases E-cadherin; reduces N-cadherin, vimentin, Slug, and Gli-1; impedes metastasis and invasion; reverses the EMT | 46 |
| Thymoquinone (TQ) | a major ingredient of Nigella sativa | PCa, CC | increases E-cadherin; decreases vimentin, Twist, ZEB1, Slug, TGF-β, Smad2, and Smad3; represses migration, invasion, and metastasis; reverses the EMT | 28, 53 |
| Unmodified gold nanoparticles | a single self-therapeutic nanoparticle | OC | upregulates E-cadherin; downregulates Snail, N-cadherin, and vimentin; inhibits the MAPK pathway; represses the EMT; suppresses tumor growth and metastasis | 58 |
| Withaferin A (WA) | a natural compound | PCa | inhibits the expression of β-catenin, vimentin, Snail, angiogenic marker factor VIII, and retic; upregulates E-cadherin; suppresses Akt signaling; induces cell death | 35 |