Target names Target gene symbol Cells Effects Possible clinical applications References 72 kDa type IV collagenase MMP2 HUVECs, tongue cancer SCC-4 cells, gastric carcinoma SNU-5 cells, lung cancer A549 cells, and U-87 glioma cells Downregulation of MMP2 mRNA and protein expression, reduced MMP-2 levels Antimetastatic [18 , 69 –72 ] Acetyl-Coenzyme A carboxylase-α ACACA HepG2 hepatoma cells Phosphorylation Antihyperlipidemic [73 ] α -FetoproteinAFP HepG2 hepatoma cells Reduced secretion of alpha fetoprotein Apoptosis [74 ] Amyloid-β (A4) precursor protein (peptidase nexin-II, Alzheimer disease) APP Neuroglioma H4 cells Reduces amyloid-β peptide (Aβ ) levels via modulation of APP Alzheimer disease [75 ] Bcl-X BCL2L1 Colonic carcinoma cells, HepG2 cells/A549 cells, prostate carcinoma cells (DU145 and PC-3, LNCaP), Jurkat cells JNK/p38 pathway and induction of ROS production. Decreased expression Cell apoptosis, anticancer, and anti-inflammatory [19 –21 , 30 , 76 , 77 ] Arylamine
-acetyltransferase 1 NAT Leukemia HL-60 cells, colon tumour cells, brain tumour cells (G95/VGH and GBM 8401) Decrease in
-acetyltransferase (NAT) protein and expression of mRNA Anticancer (leukemia, colon cancer, brain tumour, etc.) [78 –80 ] ATP-binding cassette subfamily G member 2 ABCG2 MCF-7 breast cancer cells Decrease in ABCG2 expression Breast cancer [81 ] Baculoviral IAP repeat-containing protein 2 (antiapoptosis factor c-IPA-1) BIRC2 Jurkat cells, colonic carcinoma cells (SW620) Suppresses expression of antiapoptosis factor IAP1 Anticancer [19 , 77 ] Baculoviral IAP repeat-containing protein 3 BIRC3 Jurkat cells Suppresses expression of antiapoptosis factor IAP2 Anticancer [77 ] Baculoviral IAP repeat-containing protein 5 (Survivin) BIRC5 Jurkat cells Suppresses expression of survivin Anticancer and anti-inflammatory agent [77 ] B-cell CLL/lymphoma 2 BCL2 HepG2 cells, oral squamous cell carcinoma, tongue cancer SCC-4 cells, colonic carcinoma cells, lung cancer cells, breast cancer MCF-7 (estrogen receptor+) cells, prostate carcinoma cells (DU145 and PC-3, LNCaP), activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) Bcl-2 Downregulation Cell apoptosis, cancer, and ER antagonist adjuvant therapy [19 –23 , 30 , 34 , 82 , 83 ] B-cell lymphoma 3-encoded protein Bcl-3 Gastric carcinoma SNU-5 cells Downregulation of Bcl-3 Gastric cancer [24 ] Bcl2 antagonist of cell death BAD Human oral squamous cell carcinoma Increased expression of proapoptotic BAD protein Antitumour [23 ] BCL2-associated X protein BAX Gastric carcinoma SNU-5 cells, prostate carcinoma cells (DU145, PC-3, LNCaP and PWR-1E), leukemia HL-60, tongue cancer SCC-4 cells, lung cancer cells, activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) Upregulation of Bax, increased expression. G2/M phase arrest Cell apoptosis, gastric cancer [18 , 20 , 21 , 24 , 29 , 30 , 83 , 84 ] BH3-interacting domain death agonist p11 BID Colonic carcinoma cells/HepG2 cells JNK/p38 pathway and induction of ROS production Induction of apoptosis [19 , 76 ] C/EBP homologous protein (CHOP) or growth arrest- and DNA damage-inducible gene 153 (GADD153) or DNA damage-inducible transcript 3 GADD153/DDIT3 Cervical cancer Induced expression of GADD153 Cervical cancer [85 ] CASP8 and FADD-like apoptosis regulator subunit p12 CFLAR/cFLIP Jurkat cells Suppresses expression of cFLIP Anticancer and anti-inflammatory [77 ] Caspase 3 CASP3 Tongue cancer SCC-4 cells, neuroblastoma (SK-N-SH), glioblastoma T98G cells, gastric carcinoma SNU-5 cells, HL-60 cells, prostate carcinoma cells (DU145, PWR-1E, PC-3 and LNCaP), colonic carcinoma cells, hepatoma cells, oral squamous cell carcinoma, promonocytic U937 cells, lung cancer A549, H1301 cells, activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs), BIU-87 and T24 bladder cancer cells Activation of caspase-3, G2/M phase arrest Anticancer [18 –21 , 23 –25 , 30 , 33 , 76 , 83 , 86 –89 ] Caspase 8 CASP8 Tongue cancer SCC-4 cells, colonic carcinoma cells, hepatoma cells, oral squamous cell carcinoma Activated caspase 8 Anticancer [18 , 19 , 23 , 76 ] Caspase 9 CASP9 Tongue cancer SCC-4 cells, glioblastoma T98G, oral squamous carcinoma, promonocytic U937 cells, prostate carcinoma cells (DU145 and PC-3, LNCaP), activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs), BIU-87 and T24 bladder cancer cells Activation of caspase 9 Cell apoptosis, anticancer [18 , 21 , 23 , 30 , 33 , 83 , 86 , 87 , 89 , 90 ] Cdc42 effector protein 1 CDC42EP1 Nasopharyngeal carcinoma (HONE1) cells Suppression of Rho GTPases activation (Cdc42) Cancer metastasis inhibition [91 ] Cell division protein kinase 6 CDK6 Prostate carcinoma cells (DU145 and PC-3, LNCaP), activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) Decrease in Cdk6 Cell apoptosis, cancer [21 , 30 , 83 ] Cellular tumor antigen p53 TP53 Gastric carcinoma SNU-5 cells, osteosarcoma Increased expression of p53 protein, cell cycle arrest at G1G2/M phase arrest Anticancer (gastric cancer, osteosarcoma) [24 , 92 ] Chemokine (C-C motif) ligand 2 (monocyte chemotactic protein-1) CCL2 Retinal pigment epithelial cell line Inhibits CCL2 (MCP-1) expression Anti-inflammatory [93 ] Cyclic AMP-dependent transcription factor ATF-3 ATF3 Colorectal cancer cells Induces ATF3 expression Colorectal cancer [94 ] Cyclin-dependant kinase 1/cell division control protein 2 homolog CDK1/CDC2 HL-60 cell, gastric carcinoma SNU-5 cells Inactivation of Cdc2 (CDK1) or decreased protein expression Antiproliferative and proapoptotic [24 , 95 ] Cyclin E1 CCNE1 Neuroblastoma (SK-N-SK), glioblastoma T98G cells, activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) Decrease in cyclin E Anticancer [25 , 83 , 90 ] Cyclin-dependent kinase 2 CDK2 Neuroblastoma (SK-N-SK), glioblastoma T98G cells, prostate carcinoma cells (DU145 and PC-3, LNCaP), activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) Decrease in Cdk2 Cell apoptosis, anticancer [21 , 25 , 30 , 83 , 90 ] Cyclin-dependent kinase 4 CDK4 Neuroblastoma (SK-N-SK), glioblastoma T98G cells, prostate carcinoma cells (DU145 and PC-3, LNCaP), activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) Decrease in Cdk4 Cell apoptosis, anticancer [21 , 25 , 30 , 83 , 90 ] Cyclin-dependent kinase inhibitor 1 (p21) CDKN1A Brest cancer MCF-7 (estrogen receptor+) cells, epidermoid carcinoma A431 cells, activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) Increased expression of p21 Breast cancer, ER antagonist adjuvant therapy [21 , 30 , 82 , 83 ] Cyclin-dependent kinase inhibitor 1B (P27/KIP1) CDKN1B Epidermoid carcinoma A431 cells, activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) Increased expression of Cdki proteins Cell apoptosis, cancer [21 , 30 , 83 ] Cytochrome c-1 CYC1 Tongue cancer SCC-4 cells, colonic carcinoma cells, promyelocytic leukemia HL-60 cells Release of cytochrome c-1 Anticancer [18 , 19 , 84 , 86 ] CYP2C9 CYP2C9 Recombinant CYP Inhibition of CYP2C9 Drug interactions [96 ] CYP2D6 CYP2D6 Recombinant CYP Inhibition of CYP2D6 Drug interactions [96 ] CYP3A4 CYP3A4 Caco-2 cells, patients CYP3A4 Downregulation and inhibition Drug interactions [97 , 98 ] Dipeptidyl-peptidase 4 (CD26, adenosine deaminase complexing protein 2) DPP4 Recombinant DPP4 Inhibition of DPP4 — [99 ] Early activation antigen CD69 CD69 Human peripheral lymphocytes Reduced expression of CD69 Immunosuppressive agent [100 ] Epidermal growth factor receptor EGFR Brest cancer MCF-7 (estrogen receptor+) cells EGFRdownregulated Breast cancer, ER antagonist adjuvant therapy [82 ] Ezrin EZR Nasopharyngeal carcinoma 5–8F cells Ezrin inhibition Anticancer [26 ] G1/S-specific cyclin-D1 CCND1 Giant cell carcinoma cell line, HL-60 cell, prostate carcinoma cells (DU145 and PC-3, LNCaP), Jurkat cells, neuroblastoma (SK-N-SK), activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) Inhibits expression of cyclin D1 Antiproliferative and proapoptotic, anticancer, anti-inflammatory [21 , 25 , 30 , 32 , 77 , 83 , 95 ] G1/S-specific cyclin-D2 CCND2 Prostate carcinoma cells (DU145 and PC-3, LNCaP), activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) Decrease in cyclin D2 Cell apoptosis, cancer [21 , 30 , 83 ] G1/S-specific cyclin-E1 CCNE1 Prostate carcinoma cells (DU145 and PC-3, LNCaP), activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) Decrease in cyclin E Cell apoptosis, cancer [21 , 30 , 83 ] G2/mitotic-specific cyclin-B1 CCNB1 Gastric carcinoma SNU-5 cells Decreased cyclin B, G2/M phase arrest Cell apoptosis, anticancer [24 ] Glucagon-like peptide (GCG/GLP-1/GLP-2) GCG NCI-H716 cells Enhanced glucagon-like peptide (GLP)-1 Antidiabetic agent [42 ] Growth/differentiation factor 15 (NAG-1) GDF15 Colorectal cancer cells Induces NAG-1 expression Colorectal cancer [94 ] Hypoxia-inducible factor 1α HIF1A HUVECs, HepG2 cells Prevention and reduction of HIF-1 alpha expression Tumour angiogenesis [101 , 102 ] Induced myeloid leukemia cell differentiation protein Mcl-1 MCL1 Oral cancer cells Inhibition of Mcl-1 expression Induced apoptosis [103 ] Inhibitor of NF-κ B kinase subunit alpha (Iκ B kinase) CHUK(IKK) Jurkat cells Inhibition of Iκ B kinase (IKK) Anticancer and anti-inflammatory agent [77 ] Interferon-γ IFNB1 Brest cancer MCF-7 (estrogen receptor+) cells IFN-beta upregulated Breast cancer, ER antagonist adjuvant therapy [82 ] Interleukin 8 IL8 Retinal pigment epithelial cell line Inhibits IL-8 expression Anti-inflammatory [93 ] Interleukin-1β IL1B Fibroblasts (HFL1) Induces IL-1B productions Pulmonary inflammation [104 ] Interleukin-2 receptor α -chain IL2RA/CD25 Human peripheral lymphocytes Reduced expression of CD25 Immunosuppressive agent [100 ] Interleukin-6 IL6 Keratinocytes Reduces and IL-6 expression Antiskin ageing agent [105 ] Low-density lipoprotein receptor (familial hypercholesterolemia) LDLR HepG2 cells Increased mRNA and protein expression Hyperlipidemia [106 –108 ] Matrix metallopeptidase 1 (27 kDa interstitial collagenase) MMP1 Dermal fibroblasts, U-87 glioma cells MMP-1 expression decreased Antiskin ageing agent, anticancer [70 , 109 ] Matrix metallopeptidase 9 (gelatinase B, 92 kDa gelatinase, 92 kDa type IV collagenase) MMP9 Tongue cancer SCC-4 cells, keratinocytes, gastric carcinoma SNU-5 Inhibition Anticancer [34 , 70 , 105 ] Matrix metalloproteinase-16 MMP16 Jurkat cells Suppresses expression of MMP-16 Anticancer and anti-inflammatory agent [77 ] Mitogen-activated protein kinase 3 ERK1/MAPK3 Peripheral blood monocytes (PBMC) ERK1 protein expression inhibition Antiatherosclerotic effects [110 ] Mitogen-activated protein kinase 4 ERK2/MAPK4 Peripheral blood monocytes (PBMC) ERK2 protein expression inhibition Antiatherosclerotic effects [110 ] Mitogen-activated protein kinase 8 (JNK) MAPK8 Peripheral blood monocytes (PBMC) Jun N-terminal kinase (JNK) protein expression inhibited at high levels of BBR Antiatherosclerotic effects [19 , 110 ] M-phase inducer phosphatase 1 CDC25A HL-60 cell Phosphorylation and degradation of Cdc25A Antiproliferative and proapoptotic [95 ] Multidrug resistance protein 1 (P-gp, P-gp-170) ABCB1 Tumour cell lines Significant inhibited P-gp multidrug resistance (MDR) activity MDR activity reversal [111 ] Hepatoma Upregulated multidrug resistance transporter (P-gp-170) expression Reduced retention of chemotherapeutic agents [112 ] Myc proto-oncogene protein MYC U-87 glioma cells Myc level decreased Malignant glioma and cancer development [71 ] NF-κ B inhibitor-α NFKBIA Lung epithelial cells (A-549) Inhibition of κ B-α phosphorylation and degradation Pulmonary inflammation [104 ] Nuclear factor NF-κ B p50 subunit (NF-κ B) NFKB1 Jurkat cells, osteoblastic cells, HepG2 cells Inhibit NF-κ B production and suppress NF-κ B Anticancer and anti-inflammatory agent, alcohol liver disease, osteoclast formation [77 , 113 –115 ] Nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) NR3C1 HepG2 cells Reduced GR levels Cell growth arrest [74 ] Nucleophosmin (nucleolar phosphoprotein B23) and telomerase NPM1 Leukemia HL-60 cells Downregulation of nucleophosmin/B23 and telomerase activity Cancer [116 ] Peroxisome proliferator-activated receptor-γ PPARG Free-fatty-acid-induced insulin resistance muscle cells-L6 myotubes, 3T3-L1 preadipocytes Decreased expression Antidiabetic [37 , 117 ] Platelet glycoprotein 4 CD36/FAT Free-fatty-acid-induced insulin resistance muscle cells-L6 myotubes Decreased expression Antidiabetic [37 ] Poly (ADP-ribose) polymerase family, member 1 PARP HepG2 cells/hepatoma cells, colonic carcinoma cells, prostate cancer cells (PC-3), prostate carcinoma cells (DU145 and PC-3, LNCaP), activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) Cleavage of poly (ADP-ribose) polymerase. Activation of PARP Cell apoptosis, Anticancer [19 , 21 , 22 , 30 , 76 , 83 , 87 ] Potassium voltage-gated channel subfamily H member 2 KCNH2/HERG1 Leukemic stem cells (LSCs) Inhibits HERG1 K (+) channels of leukemic cells Inhibits AML cell migration [35 ] Processed sterol regulatory element-binding protein 2 SREBP2 HepG2 cells Reduction of SREBP2 Hyperlipidemia [101 ] Proprotein convertase subtilisin/kexin type 9 PCSK9 HepG2 cells Suppression of PCSK9 mRNA and protein levels Hyperlipidemia [101 , 107 ] Prostaglandin G/H synthase 2 PTGS2/COX2 Peripheral blood monocytes (PBMC), oral cancer cell lines OC2 and KB cells, breast cancer MCF-7 (estrogen receptor+) cells, Jurkat cells, colon cancer cells Decrease of Cox-2 mRNA and protein expression Antiatherosclerotic effects, anti-inflammatory, anticancer, breast cancer ER antagonist adjuvant therapy, Anticancer [27 , 77 , 82 , 103 , 110 , 118 ] Proto-oncogene tyrosine-protein kinase ROS ROS1 HUVECs Inhibition of ROS generation Protects LDL oxidation and prevents ox-LDL-induced cellular dysfunction [19 , 119 ] Ras-related C3 botulinum toxin substrate 1 RAC1 Nasopharyngeal carcinoma (HONE1) cells Suppression of Rho GTPases activation (Rac1) Cancer metastasis inhibition [91 ] Receptor tyrosine-protein kinase erbB-2 ERBB2/HER2 Brest cancer MCF-7 (estrogen receptor+) cells HER2 downregulated Breast cancer, ER antagonist adjuvant therapy [82 ] Rho-associated protein kinase 1 ROCK1/RHO Nasopharyngeal carcinoma 5–8F cells Suppression of Rho kinase activity Anticancer [91 ] Runt-related transcription factor 2 RUNX2 Osteoblast cells Promotes transcriptional activity of Runx2 Osteoblast differentiation and bone formation in osteoporosis [120 ] SDF-1-α (3–67) (SDF-1) CXCL12 Acute myeloid leukemia (AML) Reduces SDF-1 chemokine Inhibits AML cell migration [35 ] Sucrase-isomaltase (α -glucosidase) SI Caco-2 cells Inhibit alpha-glucosidase Antihyperglycaemic [39 ] Topoisomerase (DNA) I Top1 Recombinant human topoisomerase I Top1 inhibition Anticancer [121 ] Transcription factor AP-1 AP-1 Hepatoma cells, MDA-MB-231 breast cancer cells, giant cell carcinoma cell line, colon cancer cells, U-87 glioma cells, HeLa cells Inhibition of AP-1 activity, AP-1 DNA suppression Antitumor activity, Anticancer [27 , 32 , 71 , 115 , 118 , 122 –124 ] Transforming protein RhoA RHOA Nasopharyngeal carcinoma (HONE1) cells Suppression of Rho GTPases activation (RhoA) Cancer metastasis inhibition [91 ] Tumor necrosis factor-α TNFA Macrophages, fibroblasts (HFL1) Inhibition of TNF-α Anti-inflammatory [104 , 125 ] Urokinase-plasminogen activator PLAU Lung cancer A549 cells, tongue cancer SCC-4 cells Reduced urokinase-plasminogen activator (u-PA) Antimetastatic, Anticancer [34 , 72 ] Vascular endothelial growth factor A VEGFA HUVECs Prevention of VEGF expression Tumour angiogenesis [102 ] Wee1-like protein kinase Wee1 Gastric carcinoma SNU-5 cells Increased expression of Wee1protein, G2/M phase arrest Gastric cancer [24 ]
