Table 2.
Molecular mechanism of resveratrol and derivatives anticancer activity.
| Target in carcinogenetic processes | Cancer cells | Molecular pathways | Reference |
|---|---|---|---|
| Extracellular growth factors and receptor tyrosine kinases | Melanoma | EGF-R/EGF, TGF-β, Her-2, p53, TSP1, and VEGF | (16) |
| Human umbilical vein endothelial cells | NO/eNOS, NO/cGMP/PKG, IAP1 and 2, livin, and XIAP | (17) | |
| Ovarian carcinoma (Her-2+ and −) | (18) | ||
| (19) | |||
| Formation of multiprotein complexes, signal transmission and cell metabolism (red–ox) | Prostate carcinoma | PTEN/AKT, mTOR, FOXO, DNA damage leukocytic, red–ox imbalance (enzymatic and non-enxymatic mechanisms), SOD and CAT, DNA glycosylase I | (20) |
| Melanoma | (21) | ||
| Colon carcinoma | (22) | ||
| Ovary carcinoma | (23) | ||
| T cell leukemia Jurkat | (24) | ||
| Lung adenocarcinoma (+As2O3) | (25) | ||
| Biological outcomes of growth factor signaling: cell proliferation and genome instability | Oral squamous cell carcinoma | Cell cycle arrest at G2/M and at G1/S transition, cyclin A2 and cyclin B1, cyclin D1, cyclin D2 and cyclin E, CDK inhibitor-cyclin-CDK machinery, WAF1/p21, CDK2, CDK4, and CDK6 | (26) |
| Human epidermoid carcinoma | (27) | ||
| Anaplastic thyroid carcinoma | (28) | ||
| Colon carcinoma | A3 adenosine receptors, lncRNA (AK001796), TOPO2, H2AX | (31) | |
| Lung adenocarcinoma | (32) | ||
| Gliobastoma | (33) | ||
| Breast carcinoma | (34) | ||
| Non-melanoma skin cancer (+5-FLU) | (35) | ||
| Lung adenocarciomaa | BRCA1, cyclin B1, pRb, and p21 | (36, 37) | |
| Osteosarcoma | TOPO2 | (38) | |
| Colon carcinoma (+DOX) | (39) | ||
| Cytoplasmic tyrosine kinase signaling | Human embryonic kidney cell line | NF-κB, IKKα, IKK-γ, NEMO, p65, TNF-α, Ad.Egr-TNF, Egr-1 promoter, AP-1, AP-2 and cAMP, CREB, MMP-2, and miR-328 | (42) |
| Breast carcinoma | (44) | ||
| Cytokine signaling | Pancreas adenocarcinoma | (44) | |
| Human Embryonic Kidney cell line | SIRT1 | (35) | |
| (43) | |||
| (50) | |||
| (51) | |||
| Integrin signaling | Osteosarcoma | JNK, p38 MAPK, GADD45α, ERK/JNK-ElK-1, CArG, Egr-1 AP-1/JunD, MMP-1, iNOS, α-MSH β-catenin, c-kit, and MITF | (52, 53) |
| Lung adenocarcinoma | (54) | ||
| Pancreas adenocarcinoma | EMT: MMP-1, PI-3K/Akt/NF-κB, E-cadherin, N-cadherin, vimentin, MMP-2 and MMP-9, phospho-Akt and phospho-NF-κB, TGF-β, α5β1 integrins, hyaluronic acid, Snail, E-cadherin, and N-cadherin | (56) | |
| Colon–rectum adenocarcinoma | (27) | ||
| Gastric carcinoma | (33) | ||
| (53) | |||
| (55) | |||
| (56) | |||
| Developmental signaling pathways | Colon–rectum carcinoma | Wnt: Wnt2; Notch: TTF1, TTF2, Pax8 | (57) |
| Ovarian carcinoma | Notch: Notch1, NIS, Notch1 activation-dependent p53 | (58) | |
| Gastric carcinoma | STAT3: Erk1/2(MAPK), pSTAT1 | (59) | |
| Cervix adenocarcinoma and squamous cell carcinoma | Hh: GL1, Ihh, Ptch and Smo, PKC α and δ | (16) | |
| (53) | |||
| Thyroid carcinoma | (60) | ||
| Glioblastoma | |||
| Signal transduction by the transforming growth factor | Melanoma | TGF-β, TGF-β1/Smads | (17) |
| Pancreas adenocarcinoma | (23) | ||
| Colon–rectum carcinoma | (24) | ||
| Prostate carcinoma | (27) | ||
| Apoptotic pathways | Nasopharynx carcinoma | (29) | |
| Fibrosarcoma | (30) | ||
| Liver carcinoma | (31) | ||
| Hepatoma | Bcl-2, Bcl-X(L), survivin, Bax, Bak, PUMA, Noxa, Bim, TRAIL-R1/DR4 and TRAIL-R2/DR5, cytochrome c, Smac/DIABLO, and AIF | (38) | |
| Human epidermoid carcinoma | (43) | ||
| Ovarian carcinoma | CASP (3, 8, and 9), PARP-1, myeloid cell leukemia 1 phospho-ERK and phospho-p38 expression | (61, 62) | |
| Colon–rectum carcinoma cells | (64) | ||
| Colon–rectum carcinoma (DOX) | Atg5, Atg7, Atg9, and Atg12 proteins | (65) | |
| Lung (+As2O3) | p53, pRb-E2F/DP, Fas, FasL | (29) | |
| Non-melanoma skin cancer cell (+CIS) | Fas, Fas ligand, extracellular-signal-regulated kinases (ERK) ½, and p38 expression | ||
| Liver carcinoma | |||
| Fas/APO-1 | |||
| Inflammatory pathway | Colon–rectum carcinoma | COX-2, NF-κB, AP-1, IL-6, IL-8, TNF-α, ICAM-1, MCP-1, miRNAs, and PPAR | (15, 66, 67) |
| (68) | |||
| (69) | |||
| Immune surveillance | Splenocytes | IFN-γ, CD206, CD204, IL-10, TGF-β, EGF, MMP-9, IL-6, and IL-12 | (71) |
| Macrophages and tumor-associated macrophages (TAM) | |||
| Hormone signaling | Breast carcinoma | Tif2, ERα, p53, and MAPK | (70, 73) |
| Multidrug resistance | Colon–rectum carcinoma (+5-FLU) | Desmosomes, gap- and tight junctions (claudin-2) and adhesion molecules (E-cadherin – EMT) | (23) |
| Non-small cell lung cancer cells (+5-FLU) | CASP 3, MMP-9 | (32) | |
| Non-melanoma skin cancer cell (+CIS) | NF-κB, cytochrome c, Bcl-2 and Bax, Fas and FasL | (38) | |
| Lung adenocarcioma (+As2O3) | Oxidative stress, cycle arrest at G1/S phase | (43) | |
| Colon carcinoma (+DOX) | TOPO2 | (64) | |
| (38) |
aIn italics are reported negative results (lack of anti-cancer activity on the selected target).